EXPERIMENTAL RESEARCHES. EXPERIMENTAL RESEARCHES 
ON 
CICATRIZATION IN BLOODVESSELS 
AFTER LIGATURE. 
BY 
N. SENN, M.D., 
OF MILWAUKEE, WISCONSIN. 
Extracted from the 
Transactions of the American Surgical Association, 
Vol. II. 1884. 
PHILADELPHIA: 
COLLINS, PRINTER, 705 JAYNE STREET. 
1885. EXPERIMENTAL RESEARCHES ON CICATRIZATION 
IN BLOODVESSELS AFTER LIGATURE. 
Skilful treatment of hemorrhage is an infallible criterion of 
good surgery. Dieffenbach has well said, "From the behavior 
of a surgeon in cases of severe hemorrhage are we able to judge 
of what metal he is made." The mechanical measures employed 
in the management of hemorrhage have at all times constituted 
subjects of special interest to surgeons. Presence of mind, a 
steady hand, prompt action, an accurate anatomical knowledge, 
familiarity with the various Hfemostatic agents, and clear ideas 
on the process of cicatrization in vessels, are prerequisite condi- 
tions of success in the treatment of the most frequent, and, at 
the same time, the most alarming emergency which presents 
itself to the surgeon-hemorrhage. 
Ignorance, hesitation, and timidity, in the event of sudden, 
unexpected, and alarming hemorrhage, only too often mean 
death, while, on the other hand, the exercise of skill founded on 
knowledge is often the means of saving human life under the 
most desperate circumstances. For the benefit of suffering 
humanity fear of hemorrhage has deterred pretenders from per- 
forming bloody operations, which has left the cultivation of the 
field of operative surgery to men of skill and science. 
Perhaps no branch of surgery has reached a higher degree of 
perfection than the treatment of injuries and diseases of the blood- 
vessels. The bold operations which have characterized the pre- 
sent era of surgery owe their inception and their legitimacy to 
the aseptic ligature. The aseptic ligature and the antiseptic 
treatment of wounds have rendered secondary hemorrhage an 6 
exceedingly rare accident after operations. Every surgeon of 
the late war of the rebellion is painfully aware of the frequency 
with which secondary hemorrhage occurred after gunshot injuries 
or any of the capital operations. Billroth reported 23 cases of 
ligation of large arteries after gunshot wounds, and of this num- 
ber in seven, or 30.4 per cent., secondary hemorrhage took place. 
Porta collected 600 cases of ligation of large arteries, including 
the aorta, innominata, carotid, subclavian, axillary, common iliac, 
external iliac, and femoral; of this number 75, or 12.5 per cent., 
were followed by secondary hemorrhage. Pilz has published a 
table of ligation of the common carotid artery where the opera- 
tion was done 158 times for hemorrhage; of these cases 35, or 
33.5 per cent., suffered from secondary hemorrhage, which proved 
fatal in 16, or 15 per cent. How different the results of to-day! 
An artery is ligated, the ligature is cut short, the wound heals 
by primary union, and permanent obliteration of the vessel is the 
rule. The aseptic ligature, wherever and whenever it can be 
applied, has almost entirely displaced all other haemostatic agents, 
and is now universally acknowledged as the safest and most 
reliable measure in securing provisional and definitive closure 
of vessels. Like all material improvements, it has met with 
opposition, but a more extended trial has silenced criticism. 
Every surgeon should be in possession of clear and definite ideas 
of the processes which nature employs in effecting cicatrization 
in bloodvessels after ligature, so as to qualify him to select and 
apply the various haemostatic agents intelligently, and to mea- 
sure their effect by well-defined anatomico-pathological prin- 
ciples. 
This subject has for a long time furnished a fertile field for 
theoretical speculations, pathological investigations, and experi- 
mental research. 
For more than forty years the doctrine has been prevalent 
that definitive closure of a vessel after ligature is invariably due 
to the formation and organization of a thrombus. The doctrine 
is still taught by many of our teachers and recent text-books on 
surgery. The object of this paper is to disprove this assertion, 
and to establish the fact that the production of the intravascular 7 
cicatrix is always the result of proliferation of the stable connec- 
tive-tissue cells and endothelia of the walls of the vessel inde- 
pendently of the formation of a thrombus. The various theories 
which have been advanced to explain the process of obliteration 
in vessels will be briefly mentioned in their proper order, and 
the results of different methods of experimentation will be de- 
scribed, and, finally, the results of my own experimental work 
will be noticed, thus bringing the whole subject of cicatrization 
in bloodvessels after ligature before the Fellows of the Associa- 
tion for further consideration and discussion. 
I. History of the Ligatured 
For a better elucidation of our subject it is necessary to briefly 
pass in review the history of the ligature, as it will reflect in a 
true light the pathological ideas entertained by surgeons at dif- 
ferent times regarding its immediate and remote effects in arrest- 
ing the circulation in a vessel after ligation. 
The history of the ligature has been variable and eventful, and 
has always been intimately connected with the history of surgery, 
ever constituting a reliable barometer indicating the status, the 
rise and fall, in the art and science of surgery. Its use as a 
haemostatic agent was not the result of reasoning or logical de- 
duction, but was prompted by instinct. It was used and described 
long before the circulation of the blood was discovered. The 
discovery of the circulation, anatomico-pathological investiga- 
tions, experimental researches, and clinical observations, have 
all been contributing in rescuing this invaluable agent from the 
dark domain of empiricism, and have secured for it a position as 
a remedial agent second to none in points of importance, relia- 
bility, and frequency of use. 
The first account of the application of a ligature for the pur- 
1 In the preparation of this part of the paper I am greatly indebted to the follow- 
ing articles: W. Greifenberger, Historisch-kritische Darstellung der Lehre von den 
Unterbindung der Blutgefasse. Deutsche Zeitsch. f. Chir., vol. xvi. A. Adam- 
kiewicz, Die mechanischen Blutstillungsmittel bei verletzen Arterien, von Pare bis 
auf die reneste Zeit. Archiv fur Klin. Chir., vol. xiv. 8 
pose of preventing hemorrhage is given by Sus'rutas, a disciple 
of the divine Dhavantari in his Ayur Vedas (1500 B. C.), who 
tied the umbilical cord in newly-born infants, with a string, eight 
inches from the navel previous to cutting it. A number of writers, 
among them Platner, Holtze, Langenbeck, and Fischer, allude 
to Hippocrates (460-377 B. C.) as the discoverer of the ligature. 
They base their opinion on the following passage from his works, 
translated into Latin by Fassius:1 "Sanguinem e renis profluen- 
tem sistunt animi deliquium, figura aliorsum tendens, venae inter- 
ceptio, linamentum contortum, appositio, deligatio." 
Archigenes (100 B. C.) made free use of the ligature after 
amputations. Celsus (30-25 B. C., 45-50 A. D.), in his works, 
refers to the ligature as a well-known remedy, and credits an 
obscure physician of the Alexandrian school with its discovery. 
Celsus used the ordinary linen thread, and gave particular indi- 
cations for its use and manner of application. In speaking of 
the operation for hydrocele, he says :2 " Nervus, ex quo testiculus 
dependet, praecidendus; post id venae et arteriae ad inguen lino 
deligandcc et infra vinculum abscindendae sunt." 
Galen (131-211 A. D.), although no practical surgeon him- 
self, yet familiar with the literature of that day, frequently men- 
tions the ligature, and gives particular directions to apply it to 
the proximal end of the bleeding vessel. For ligature material 
he advises silk and fine catgut. The definite closure of the vessel 
he attributed to the action of the tissues surrounding it, as is 
evident from the following quotation:3 "Quae namque caso in 
abscisis vasorum partibus coalescit, ea pro opercula est ac oscu- 
lum eorum claudit." The name of Antyllus (350 A. D.) occu- 
pies such a prominent position in vessel surgery, and his method 
of procedure in cases of aneurism is so familiar to every student 
in surgery, that more than a simple allusion to his name would 
appear superfluous. 
1 Hippocratis medicorum omnium facile principis opera omnia quae exstant. 
Frankf. ii. p. 1194. 
2 Aul. Corn. Celsi de medicina libri octo, quos ad Leon. Targae recens, de J. H. 
Waldeck, Munster, 1827, p. 150. 
8 Claudii Galeni opera omnia. C. G. Kuhn, Lipsise, 1827, T. x. L. iii. cap. xxii. 
p. 941. 9 
Paulus /Egineta (625-690, A. D.) treats extensively of the 
ligature, quoting freely from the writings of Celsus and Galen. 
In -practising ligation of vessels as a therapeutical measure in 
diverse affections he passed two ligatures beneath the vessel 
with the aid of a needle, cut the vessel between them, and, after 
permitting the requisite amount of blood to escape, closed each 
end of the vessel separately. Rhazes (850-922, A. D.) mentions, 
as a last resort to arrest hemorrhage from large vessels, the liga- 
ture which he made of strong linen thread. 
The prolific writer, Avicenna (980-1037, A. D.), disposes of 
the subject of ligation of vessels briefly thus fl " Quod si (sc. 
vena) fuerit pulsatilis, turn melius est ut veles earn cum filio 
lini, et similiter si fuerit ron pulsatilis, verum tamen multoties 
elevatur sanguis ejus." Aneurisms he treated in accordance 
with the teachings of Antyllus. He limits ligation to arteries, 
believing that bleeding from veins is arrested spontaneously or 
yields to the use of the customary styptics. 
Avenzoar (1113-1162 or 1196, A. D.) and Averroes (1198) 
were familiar with the ligature. The latter, in his commenta- 
ries on the writings of Avicenna, directs that in performing 
arteriotomy the vessel should be surrounded by two ligatures 
before it is divided. 
Roland (1252), a pupil of Roger, of Parma (1214), again men- 
tions the use of the needle in applying the ligature, a practice 
followed by most of the prominent Italian surgeons at that time. 
Bruno, of Castel Longobrugo (1252), pointed out the differ- 
ence between arterial and venous hemorrhage, and gave the 
advice, in case the bleeding could not be arrested by any other 
means, to seize the artery or vein with a small hook and carry 
a thread with a needle around the vessel and tie it firmly. 
Guy de Chauliac (1300-1363, A. D.) prefers the ligature when 
the artery is deeply seated, in which case it is well brought into 
view, and that end is firmly tied which is placed towards the 
heart or liver. 
1 Avicennae Arabum medicorum principis Canon medicinae, ex Gerardi Cremo- 
nensis versione per Fabium Paulinum Utinensem. Venetiis apud Juntas. 1595, 
Lib. iv. Tract. II. cap. 17. 10 
Lenardo Bertapaglia (died 1460) modified the intermediate 
ligation by passing the needle armed with a double thread not 
under, but through the artery, tying both ligatures firmly over 
each other. Giovanni Vigo (1460-1520), the founder of the 
school of surgery in Rome, was acquainted with the direct or 
immediate ligature, but gave preference to the intermediate 
method of ligation. Alfonso Ferri described the ligature needle 
used at that time in applying the intermediate ligature, which 
was about three inches in length and curved only at the point, 
with the eye at the opposite end; the point presented four sides 
with obtuse angles, so as to prevent injury to the vessel or its 
adjacent parts. This needle was armed with a double ligature, 
and entered about 2-3 fingers' breadth from the margin of the 
wound, passed underneath the vessel, and made to emerge on 
the opposite side of the wound, and the ligature firmly tied in 
several knots. 
Angelo Bolognini (1508), founder of the school at Bologna, 
also practised percutaneous ligation of vessels, using silk as a 
ligature material. 
Jacques Houllier (1493-1562) in wounds of the arteries relied 
on digital compression, and, when this failed and the vessel was 
deeply located, he advised that it be gently drawn forward, 
slightly twisted, and, after ligating both ends, divided completely 
at the point of injury. 
In Germany we find the first mention of the ligature by 
Hans von Pfoloprundt. Hieronymus Brunschwig (1450-1533) 
practised and described Bertapaglia's method of ligation. 
Hans von Gersdorf (1517), a military surgeon of great expe- 
rience, frequently applied the intermediate ligature in cases of 
vessel wounds, but preferred styptics and the actual cautery in 
amputations. 
Walter Ryff tied the proximal end of the vessel by isolating 
and seizing it with a small hook, and tying firmly with a silk 
ligature. 
It will be seen that, up to this time, the ligature has for the 
most part only been used as a dernier ressort in cases of wounds 
of vessels, while styptics and the actual cautery are still relied 11 
upon as the safest and easiest methods of arresting hemorrhage. 
To Ambrose Pare (1517-1590) surgery owes a great debt of 
gratitude, not as the discoverer, but as the first and most devoted 
champion of the ligature. Through his influence and untiring 
zeal the ligature gradually found its way into popular favor, and 
displaced the barbarous treatment by styptics and cautery. 
He practised both, the immediate and intermediate ligation, ac- 
cording to the location of the vessel and circumstances of the 
case. His first operations were performed about the year 1552. 
In a German translation of his work on Surgery,1 published in 
the year 1601, I find the following directions:- 
" Wo auch dieses nicht helffen wolte, so muss man die Haeflte, 
wofern deren eins oder mehr vorgangen, widerumb auffthun, 
und under der verletzten ader, gegen ihrem Anfang oder Wurtzel 
zu, mit einer Nadel und I'aden durchhin fuhren, die Ader sampt 
einer solchen portion oder stiicklein Fleisches desselbigen Orts, 
wie viel nemlich die Gelegenheit geben und erleiden mag, fassen 
und zubinden. Denn also hab ich offtmahlen sehr grosse und 
gewaltige Verblutungen, auch in denen Wunden, durch welche 
gantze Arm oder Schenkel abgehawen worden, gestillt, wie an 
seinem ort sol gemeldet werden. Dieses aber zu -verrichten, 
werden wir vielmal genotiget, die ganze Haut, so liber der Ader 
ligt, auffzuschneiden und zu entblbssen. Denn wenn eine auss 
den Blut oder Lufftadern des Halses (Jugularium) durchschnitten 
were, und sich die beyde Ende, beydes hinauff und hinabwertz 
von einander gezogen, und also verborgen hetten, muss man die 
gantze Haut unter welche sie sich verschlossen, erbffnen, die 
Ader entdecken, mit einer Nadel und Faden darunter hinfahren, 
und also zusammenbinden, wie ich dan selbst vielmahl sehr 
gliicklichen und wohl verrichtet. Du solt aber dieses Bandt 
oder Faden nicht eher auflosen, biss dass du sihest, das die Ader 
mit Fleisch iiberwachsen, und der Ader Mundlochlein verstopfet 
sey, damit das Blut nicht widerumb und von neuwen zu rinnen 
anfange." For fear of secondary hemorrhage Pare favored the 
• Wundt Artzney, od. Artzney spiegell. Translated from the Latin by Petr. 
Offenbach, Frankf. 1601, p. 372. 12 
ribbon ligature, made of a number of threads ; at the same time 
he aimed to include portions of tissue surrounding the vessel, 
and removed the ligature as soon as healthy granulations cov- 
ered the exposed portion of the vessel. He used the ligature 
with a view simply to approximate the inner walls of the vessel 
for a sufficient length of time for union to take place, when its 
further presence was considered useless and even detrimental. 
The contemporaries of Pare were slow to acknowledge the 
superiority of the ligature over the rude, but time-honored cau- 
tery. On the one hand, ignorance and prejudice combined in 
checking progress, while, on the other, it must be acknowledged 
that Fare's ligature was an exceedingly imperfect thing, which, 
when used according to his directions, could not fail to frequently 
disappoint the most ardent admirer. It required centuries tr 
establish it in the confidence of the profession. 
Jacques Guillemeau (15 50-1613 A.D.), Pare's pupil, friend, ano 
successor, labored faithfully and earnestly in the interest of the 
cause of his illustrious master. He was one of the first who re- 
sumed the operation of arteries in their continuity for the cure 
of aneurism. He applied the ligature on the cardiac side, 
opened the sac, and allowed it to heal by granulation. 
Pierre Dionis (died 1718) states that at his time the cautery 
was used almost exclusively at the Hotel Dieu after amputations, 
although he resorted to the ligature frequently, and in some 
instances even practised immediate ligation. In 1733, Petit 
(1654-1750) writes of the ligature:1 "La ligature cause des 
grandes douleurs, des tressaillements convulsifs et quelque fois 
la convulsion du Moignon, qui souvent est mortelle ou par elle- 
meme ou parcequ' elle occasionne 1'hemorrhagie par les mouve- 
ments extraordinairs que la malade ne pent s'empecher de faire." 
Fabricius von Hilden (1560-1634) and Scultetus (1595-1645) 
introduced Pare's practice into Germany. The former made 
use of the hemp ligature, but restricted its application to young 
healthy persons. 
Cornelius von Solingen (died 1692) practised immediate 
1 M6m. de l'Acad. Royale des Sciences, 1733, p. 91. 13 
ligation after the example of Dionis. Anton Nuck (died 1692) 
only made use of the ligature in operating for aneurism after 
the method of Antyllus. 
In England the ligature was introduced by Wiseman (1566- 
1625) and was eagerly adopted after the discovery of the circu- 
lation by Harvey in 1619. 
Fabricius ab Aquapendente (died 1620) applied two ligatures 
to arteries and divided the vessel between them, so as to allow 
both ends to retract. 
Marcus Aurelianus Severinus (1580-1656) was the first to tie 
the femoral artery near Poupart's ligament. 
Cesare Magati (1597-1647) followed the advice of Galen and 
Avicenna, and tied the vessel only on the cardiac side. 
Kirkland (1721-1798) attributes the definitive closure of 
vessels after ligation to the inherent contractibility of the vessel 
wall. 
White and Aikin expressed a similar view, as becomes ap- 
parent from the following passage: "That the arteries, by their 
natural contraction, coalesce as far as their first ramification."1 
John Bell (1760-1820) concurred in this view, but added 
another important element, adhesive inflammation in the vessel 
wall induced by the ligature.2 
Larrey (1766-1842) observed that in many cases after 
ligation no coagulum formed, and, in consequence, asserted that 
definitive obliteration of the vessel can take place independently 
of it, and is then due to contraction of the vessel wall. 
Richerand (1779-1840) believed that the ligature brings 
the inner walls of the vessel in contact, and that direct adhesion 
takes place, the result of adhesive inflammation. 
Garengeot (1688-1759) feared the cutting through of the 
ligature, and, for the purpose of preventing this accident, advised 
the use of a broad, ribbon-like ligature. 
Claude Ponteau (1725-1775) abandoned the use of the broad 
ligature, but, to guard against the same evil, included within the 
ligature a sufficient amount of paravascular tissue. 
1 Cases in Surgery, p. 171. 
2 Discourses on the Nature and Cure of Wounds, 1800, p. 109. 14 
Lorenz Heister (1683-1758) used a stout ligature, and tied 
over a small cylinder of lint to prevent premature cutting 
through of the ligature. 
J. Z. *Platner (1694-1747) made use of a similar contrivance, 
but always applied a double ligature with a third (reserve 
ligature) on the cardiac side, to be tied in the event of secondary 
hemorrhage. 
Alexander Monroe (1697-1767) protested against the inter- 
mediate ligature, and emphasized the importance of direct liga- 
tion. He used broad ligatures, and tied only with sufficient 
firmness to approximate the inner walls of the vessel. 
Wm. Bromfield (1712-1792) isolated the artery, drawing it 
out on the surface of the wound with a hook of his own con- 
struction, and which still bears liis name, and applied a flat 
ligature. 
In France, Deschamps (1740-1824) advocated the superiority 
of immediate ligation by means of a broad ligature, on the 
ground that when the intermediate ligature is used, the inter- 
posed tissues disappear very rapidly, leaving the ligature loose 
around the artery, thus, favoring the occurrence of secondary 
hemorrhage. 
Abernethy (1763-1831) applied a double ligature in tying 
an artery in its continuity, and divided the vessel between them, 
claiming that in doing so he was able to relieve the tension in 
the peripheral portion of the vessel, and, at the same time, enable 
both ends of the artery to retract into the tissues. He also 
condemned the reserve ligature, as it would necessitate more 
extensive isolation of the vessel, thus cutting off nutrition, and 
provoking a higher degree of inflammation and suppuration. 
August Gottleib Richter (1742-1812) introduced the imme- 
diate ligature into Germany. 
On Dec. 12, 1785, John Hunter (1728-1793), for the first time, 
tied the femoral artery in loco praedilectionis for popliteal aneu- 
rism. He applied four ligatures at short interspaces, of which 
number only the most distal one was tied firmly ; the remain- 
ing ligatures were tied in such a manner that the lumen of the 
proximal end of the artery represented a cone, with the base 15 
towards the cardiac side of the vessel. Hunter anticipated that 
this method of operation would favor the formation of thrombus, 
and thus afford additional security against secondary hemor- 
rhage. His expectations, however, were not realized, as second- 
ary hemorrhage occurred on three different occasions, and the 
patient did not recover until seven months had elapsed. He 
did not repeat this operation, and subsequently used only one 
ligature. 
Desault accidentally made the observation that in the ordinary 
method of ligation with the round ligature the two inner tunics 
of an artery are ruptured. 
This fact was verified by Jones, who, in 1806, made a series 
of careful experiments to determine this point. The classical 
work of Jones exerted a potent influence in establishing the 
claims of the ligature, not only in England but wherever sur- 
gery was practised. He claimed that obliteration of an artery 
after ligature can take place, independently of the formation of 
a thrombus, by the traumatic inflammatit? 1 and plastic exuda- 
tion induced by the ligature. In his experiments on animals he 
applied several ligatures in close proximity. He called partic- 
ular attention to the deleterious effects of suppuration on the 
process of cicatrization in the bloodvessels, and, for the purpose 
of guarding against this event, advised the removal of the liga- 
tures immediately after they had ruptured the internal coats or 
before suppuration is established. He believed that provisional 
closure of the vessel is accomplished by the lacerated tissues 
within the lumen of the vessel, and that the healing process 
within the vessel is the same as in any other wound, producing 
the definite obliteration. In tying large arteries he advised the 
double ligature and division of the vessel between. 
B. Travers adopted the views promulgated by Jones, but 
substituted the temporary for the momentary ligature. He 
recommended the removal of the ligature as soon as plastic in- 
flammation is fully established, and before suppuration has time 
to take place. The period of time in which the ligature would 
accomplish this object he placed at 48 to 90 hours, according to 
the size of the vessel which had been ligated. Jones and 
Travers deserve to be called the discoverers of the temporary 16 
ligature upon a scientific basis. On Feb. 14th, 1817, Travers, 
for the first time, put his theory into actual practice. He ligated 
the brachial artery for aneurism, and removed the ligature after 
50 hours. The case proved successful. The next case, the 
artery being the same, did not terminate so favorably; second- 
ary hemorrhage set in and proved fatal. J. Hutchinson's case, 
operated upon in a similar manner, also terminated in death by 
recurring hemorrhages. 
Sir Astley Cooper applied the temporary ligature in two in- 
stances ; the results not meeting his expectations he abandoned 
it. Among the most formidable opponents of the temporary 
ligature may be mentioned Hodgson, Vacca Berlinghieri, and 
C. J. M. Langenbeck, who claimed that it was impossible to de- 
termine the exact lertgth of time after which it would be safe to 
remove the ligature, and that the necessary manipulations for 
the removal of the ligature would interfere with the prompt 
healing of the wound. 
In Italy, Antonio Scarpa (1747-1832) strongly advocated the 
employment of the temporary ligature. He used the broad 
ligature and tied over a cylinder of lint for the purpose of bring- 
ing and keeping in apposition a large surface of the inner walls 
of the vessel. His experiments have demonstrated that obliter- 
ation of a vessel by adhesive inflammation can and does take, 
place without division of the inner coats. He compared the 
inner surface of bloodvessels with serous membranes, and cred- 
ited it with the property of undergoing the same pathological 
changes when subjected to traumatism. He ascertained that 
adhesive inflammation follows about four days after the applica- 
tion of the ligature, while the time required for suppuration to 
arise requires from one to two days longer, consequently he de- 
termined the time for the removal of the ligature in accordance 
with the general condition of the patient. In young, robust 
persons he removed the ligature on the fourth day, and in old 
or decrepit persons he allowed it to remain for six days. 
P. U. Walther asserted that definitive closure of vessels after 
ligation takes place within 40 hours, and urged that the ligature 
should be removed after the lapse of this time. 17 
In Germany, Victor von Bruns was the next and last to bring 
the temporary (amovable) ligature before the notice of the pro- 
fession. He removed the ligature after two or three days, ac- 
cording to the size of the vessel, and supports his claims for the 
superiority of this method of ligation by the results of a large 
clinical experience. 
Pecot compared the methods of Jones and Scarpa by way of 
experiment and came to the conclusion that the round ligature, 
if applied with sufficient firmness to sever the inner coats of the 
artery, excites adhesive inflammation earlier than if the broad 
tape ligature is used. 
Ponteau attributed great importance to the connective tissue 
around bloodvessels in the process of obliteration, hence he ad- 
vised that an abundance of this tissue should be included within 
the ligature. 
Delpech (1777-1832) arose against Scarpa in France, and C. 
J. M. Langenbeck in Germany. The latter regarded the adhe- 
sion of the inner vessel walls of prime importance in effecting 
permanent closure, while to the thrombus and lymph coagulum 
he assigned a less important role. The older German surgeons 
were in the habit of using hemp or linen ligatures. The silk 
ligature was first proposed in that country by Ph. Fr. von 
Walther. For the purpose of preventing the ill effects of the 
customary ligature a variety of ligature materials was proposed, 
such as chamois skin by Physick (1814), catgut by Sir Astley 
Cooper, silkwormgut by Wardrop, elastic rubber strings by 
".evert, tendons by Paul Eve, human hair by Porta. Metallic 
.igatures were brought forward as being less irritating than the 
ordinary ligature; gilt iron wire was proposed by Ollier, fine 
iron wire by B. v. Langenbeck, and silver wire by Wagner and 
Sims. Levert experimented with all kinds of metallic ligatures- 
lead, gold, silver, and platina-and always obtained primary 
union of the wound. Metallic ligatures were always cut short 
and permanently remained in the wound. * Until the end of the 
eighteenth century the ends of the ligature were brought out 
through the wound. The first attempts to cut short the ligature 
and leave it permanently in the wound were made by Lawrence, 18 
who, in 1814, published the results of his experience. For 
ligatures he used fine dentist's silk. According to Samuel 
Cooper, however, the priority of this procedure should belong 
-to a certain Haire of Essex, who is said to have practised it 
in 1786. 
Hennen adopted the practice in 1813, and within four months 
followed it in 34 cases without observing any unfavorable results. 
Delpech and Guthrie also indorsed this practice. The introduc- 
tion of antiseptic surgery has, however, wrought the greatest 
improvement in the ligature, and the founder of antiseptic sur- 
gery, Sir Joseph Lister, has also furnished us with the ideal 
ligature-the aseptic ligature. What has been sought for cen- 
turies has at last been found, a ligature which will arrest the 
circulation with safety and certainty, and a minimum amount 
of traumatism until the process of cicatrization is completed, 
and when its work is accomplished it gradually disappears by 
absorption and substitution. 
Since the introduction of the antiseptic treatment of wounds 
and the aseptic ligature, surgery has received a new impulse, 
results have been obtained which were never realized before, 
operations have been performed successfully which were pre- 
viously beyond the grasp of even the most ambitious, and, more 
than all, those horrible spectres, hospital gangrene, erysipelas, 
pyaemia, septicaemia, and secondary hemorrhage, which haunted 
the surgeons of only fifteen years ago by night and by day, 
have almost completely disappeared from hospital as well as 
private practice. For all this we are indebted to Lister. A 
variety of other animal tissues have been prepared into ligatures 
and made aseptic, and have been recommended at different times 
as substitutes for the catgut ligature. Among them we may 
enumerate silk, silkwormgut, whale and deer tendon, perito- 
neum, coats of bloodvessels, and nerve tissue. With the excep- 
tion of the first two, all of these ligature materials, if rendered 
perfectly aseptic, will, after a certain time, undergo absorption, 
but it is questionable if any of them possess any advantage over 
well-prepared catgut. Czerny is entitled to a great deal of credit 
for the improved silk ligature. He has demonstrated that when 19 
silk is made perfectly aseptic by boiling and immersion in car- 
bolized water it can be safely left in the tissues, where it becomes 
encysted. 
II. Histology of Bloodvessels. 
For our purpose it is not necessary to give a complete de- 
scription of the minute anatomy of the bloodvessels, but a brief 
allusion to the arrangement and relations of the histological 
elements is necessary, with a view to study the process of 
cicatrization after ligation; my remarks will, therefore, apply 
only to vessels of such size which the surgeon is called upon 
to ligate. Our present knowledge of cicatrix formation in 
bloodvessels we owe largely to a better understanding of the 
structure and functions of the coats of the vessels on the one 
hand, and to the laborious researches concerning tissue regene- 
ration and inflammatory tissue formation on the other. As 
arteries have been made more frequently the object of experi- 
ments than veins, we shall give a description of the arterial 
coats, and, with but few unimportant exceptions, all what can 
be said of the structure and obliterating processes in arteries 
will apply with equal force to veins. The arteries are cylindri- 
cal tubes of uniform diameter between their branches. The 
importance of their function demands that they should occupy 
such localities that would afford the greatest security against 
injuries from without and diseased processes within the body. 
In man the anatomical protection against injury and disease of 
the arterial system exists in a wonderful degree of perfection, 
the vessels, as a rule, being deeply situated in the concavities, 
depressions, and channels of bone, on the flexure side of joints, 
protected by dense fascia, supported by muscles, and, where 
location demands it, surrounded by a soft cushion of adipose 
tissue; as an additional medium of protection and source of 
nutrition they are accompanied everywhere by a sheath of con- 
nective tissue, which connects them loosely with the surround- 
ing tissues. 
The bloodvessels are a product of the mesoblast, and are 20 
composed of unstriped muscular fibres, elastic tissue, connective 
tissue, and endothelium. From an anatomical, physiological, 
and, I may add, pathological, standpoint, it has been customary 
to distinguish three coats, called respectively, according to their 
location: I. Internal or Intima; 2. Middle or Media; 3. Exter- 
nal or Adventitia. In larger arteries these coats can be sepa- 
rated and recognized without the aid of the microscope. 
I. Intima.-The intima is a delicate hyaline elastic membrane. 
In the larger arteries it is composed of a single layer of flat 
endothelial cells, a delicate layer of longitudinal bundles of con- 
nective tissue, and a network of elastic tissue. His applied 
the term endothelium to the pavement epithelium lining the 
inner walls of the bloodvessels, lymphatics, and serous cavities, 
to distinguish it from the other varities of epithelium. As found 
in the vessels, Auerbach named it perithelium, and Frey sug- 
gested the simple name of primary vessel tunic. The endothe 
lial layer is composed of eliptical or irregular polygonal cells, 
which are often elongated into a lanceolate shape, being con- 
tinuous with the endocardium on the proximal, and the capillary 
vessels on the distal side. The shape of the cells is greatly 
modified by the degree of the distension of the vessel. The 
nucleus is oval, its long axis, like that of the cell, corresponding 
to the longitudinal direction of the vessel. In the fresh state 
the contour of the cell is very faint and exceedingly difficult to 
trace without the assistance of staining. A one per cent, solu- 
tion of nitrate of silver, as first suggested by von Recklinghau- 
sen, stains the cement substance a dark brown, which imparts 
a well-defined outline to the irregular margins of each individual 
cell. If the protoplasm be at the same time stained with chlo- 
ride of gold, the picture is at once rendered beautiful and per- 
fect, illustrating the cell and its contents to perfection. The 
cement substance surrounding each individual cell is a lifeless 
substance, closely allied to the basis substance of the connective 
tissue, but it is not glue yielding. Some histologists (Heitz- 
mann, Stricker, Klein) describe a network of living matter 
within the cell which sends delicate conical offshoots through 
the cement substance, thus forming a living reticulum, which 21 
connects the individual cells and permeating the lifeless cement 
substance in every direction. These projections were first seen 
and described by Max Schultze. According to Heitzmann1 
these living prolongations are capable of producing new tissue 
elements. The stomata or stigmata in capillary vessels are 
slight defects in the irregular outlines of the cement substance, 
and are supposed to permit the passage of the morphological 
elements of the blood more particularly when in a condition of 
inflammation. " The attachment of endothelia to the subjacent 
connective tissue is either direct, by means of delicate filaments 
penetrating the rim between the feet of the endothelia and the 
neighboring fibres of connective tissue ; or it is indirect by means 
of an intervening basement layer."2 The outer surface of this 
basement membrane in many instances is found to be covered 
by a layer of flat, polyhedral cells discovered by Czerny by 
means of silver staining. These cells may be regarded as endo- 
thelia. These endothelial or endothelioid cells may bear impor- 
tant relation to the subject of regeneration of endothelia. Frey3 
acknowledges that we are as yet ignorant concerning the repro- 
duction of endothelia, while Wendt4 attributes to the vascular 
endothelia the still higher function of being converted into ele- 
ments identical to leucocytes after separation by desquamation. 
This process has been actually observed by Altmann in the serous 
endothelia of the exposed mesentery of a frog.5 The absence 
of a direct blood supply does not appear to deprive them of a 
sufficient nutritive supply by means of which they receive their 
own nourishment, and which imparts to them the power of repro- 
duction and to assume an active part in various pathological 
processes. In large arteries immediately underneath the lining 
endothelium there is a special connective-tissue membrane 
variously designated as striated internal coat (Kblliker), inner- 
1 Microscopical Morphology of the Animal Body in Health and Disease. New 
York, 1883. 
2 Ibid, page 318. 
3 Handbuch der Histologie und Histschemie des Menschen. Leipzig, 1874, 
p. 147. 
4 The Bloodvessels. Satterthwaite's Manual of Histology. N. Y. 1881. 
6 Archiv fur Mikrosk. Anatomie, vol. xvi. p. 3. 22 
most longitudinal fibrous coat (Remak), and internal fibrous 
coat (Eberth). In the adult this layer is distinctly fibrillated. 
Embedded in this membrane are lodged numerous branching 
corpuscles, containing large, conspicuous nuclei and so-called 
granulation-bodies. Wendt regards the granulation bodies as 
matrix-cells for the regeneration of desquamated endothelia. 
Talma has described similar bodies, but regarded them as the 
product of endothelia, instead of vice versa. This inner connec- 
tive-tissue membrane is prolonged into the smaller arterial 
branches in the form of a single layer of branched cells being 
interspersed between the endothelial lining and the elastic mem- 
brane of the intima. The elastic membrane of the intima con- 
sists of a network of longitudinal fibres. In the larger arteries 
this membrane is laminated, the lamina being (longitudinal) 
fenestrated elastic membranes, between which pass (longitudi- 
nal) networks of elastic fibres. 
II. Media.-The middle coat consists of unstriped muscular 
fibres, elastic and connective tissue. In vessels of small or 
medium size, there is a preponderance of muscular over elastic 
elements, in the larger trunks the reverse condition obtains. 
The muscular tissue consists of smooth nucleated muscle fibres 
arranged in concentric layers, and disposed transversely or 
obliquely around the vessel. Bardeleben maintained that an 
inner longitudinal muscular coat exists in all large and middle- 
sized arteries. The muscular elements are arranged in layers 
or groups, the interspaces being occupied by connective tissue 
and elastic fibres arranged in networks. The complicated rela- 
tions of the elastic fibres in this coat have caused no little con- 
fusion in giving a description of it. 
Henle describes four distinct layers. The middle coat is dis- 
tinctly separated from the intima by the interposition of the 
internal elastic coat. The external elastic coat of the media 
consists of a close network of delicate elastic fibrils anastomos- 
ing with similar reticula from the adventitia. The third layer 
of the elastic tissue fills the interspaces between the muscular 
layers in the interior of the middle coat. A small amount of 
connective tissue is found in this coat chiefly accompanying 23 
small bloodvessels when they permeate it. The elastic fibres 
are usually arranged transversely to correspond with the direc- 
tion of the muscular fibres, but some of them especially those 
in immediate contact, and intimately connected with the fenes- 
trated membrane of Henle, are arranged in a longitudinal 
direction. The great degree of elasticity possessed by the arte- 
rial coats is usually wrongly attributed singly to the existence 
of the elastic tissue, and Hyrtl1 very properly remarks that all 
of the tunics share this property in common with the elastic 
tissue, otherwise the remaining tissues would suffer a certain 
amount of distraction during the expansion of the vessel. The 
circular direction of the muscular fibres, and the same direction 
of the bulk of the elastic fibres of the middle coat, predispose 
to the laceration of this coat in ligating an artery by means of 
a round ligature when firmly applied; but, as some of the fibres 
are arranged obliquely and longitudinally, complete division 
occurs but seldom, and only on the application of considerable 
force. The principal elements of this coat, in common with 
the same tissues in other localities in case of injury or disease 
affecting their structure, do not possess the power of reproduc- 
tion or regeneration. The loss of tissue is filled in by cicatricial 
tissue, and solutions of continuity are invariably repaired by 
connective tissue. 
III. Adventitia.-The external coat, the adstitia of Haller, is 
the simplest in structure, being composed of interlacing bundles 
of connective tissue, commingled with elastic lamellae of vary- 
ing thickness. The external coat serves as a nidus for the 
nutrient vessels, the vasa vasorum. These vessels only in ex- 
ceptional cases (Henle) arise from the trunk which they supply, 
but are usually recurrent vessels from the nearest branches. 
Hyrtl has called attention to the fact, that even the smallest of 
these vessels are accompanied by two veins. He has never 
seen these vessels extend beyond the adventitia. Frey asserts 
that the media receives vessels from the adventitia. In the 
outer coat the vessels resemble the capillaries in the connective 
tissue only forming a more dense vascular network. 
1 Lehrbuch der Anatomie des Menschen, Wien, 1878, p. 140. 24 
Klein locates the vasa vasorum as follows : " The media and 
adventitia of large vessels (arteries and veins) contain a special 
system of nutrient bloodvessels, vasa vasorum; the arterial and 
venous branches of these lie chiefly in the adventitia, occasion- 
ally also in the part of the media; the capillaries generally 
penetrate into the media and near the intima, only seldom also 
into the latter (Koster). In the microscopic arterial branches 
we meet with capillary vessels, as a rule only in the adventitia."1 
Flint says: " A tolerably rich plexus of vessels is found in 
the external coats of the arteries. These are called vasa 
vasorum, and come from the adjacent arterioles, having no 
direct connection with the vessel on which they are distributed. 
A few vessels penetrate the external of the middle coat, but 
none are ever found in the internal coat."2 
Lymph-spaces arc present as intercommunicating interfas- 
cicular spaces, containing connective-tissue cells, in all coats of 
arterial and venous trunks. Most histologists take it for granted 
that the ultimate distribution of nerve - filaments from the 
cerebro-spinal centres and the sympathetic reach only the 
adventitia and media. Cohnheim's researches, however, tend 
to prove that the finest axis-fibrilli of the nerves terminate in 
the epithelial layers. The termination was described by some 
observers as a plexus between the epithelia, while others 
(Pflueger, Flemming) claim that the axis fibrilli penetrate the 
body of the epithelium and may terminate in its nucleolus. 
Heitzmann has traced the terminal filaments into the cement 
substance between the epithelia. From the foregoing anatomi- 
cal consideration, it is evident that the intima, although devoid of 
bloodvessels, yet receives sufficient nutritive supply which renders 
it capable to regenerate its own elements in case of loss, and to 
assume inflammatory changes under the same circumstances 
and in the same manner as other tissues occupying the same 
relative position to the vascular system. I will append a short 
abstract of the microscopical description of veins as given by 
1 Atlas of Histology, Phila. 1880, p. 144. 
2 The Physiology of Man, N. Y. 1866, vol. i. p. 245. 25 
Raab as an introduction to his paper "On the development 
of the cicatrix in bloodvessels after ligation." His studies were 
made on veins of dogs. On making a longitudinal and a trans- 
verse section through a vein, the endothelial cells appear as an 
exceedingly delicate seam which, from the greater prominence 
of the nuclei towards the lumen of the vessel, presents a 
slightly wavy appearance. The endothelial cells are not in 
direct contact, but each is surrounded by a zone of cement sub- 
stance which fastens the cells among themselves and to the 
subjacent tissue. This cement substance, according to Julius 
Arnold, is a remnant of the protoplasm from which the original 
cells were formed. The nucleus containing a number of nucleoli 
is located near the centre of the cell. On section this nucleus 
presents the outlines of a half ellipse, the long axis of which is 
in contact with the vessel wall. The distance between two 
nuclei of neighboring cells amounts to three or four times their 
longest diameters, and from this it is easy to estimate the area 
of a protoplasmic plate. As carmine stains only the nucleus, 
the contour of a cell can only be traced after staining the speci- 
men with nitrate of silver. The endothelia are either rhom- 
boidal or polygonal in shape. Isolated cells can be obtained in 
most perfect condition from veins which have been immersed 
for some time in a one per cent, solution of chloride of sodium, 
lime-water, or Mueller's fluid. For silver staining, the valves 
are best adapted; they can be spread on the object glass with- 
out any special preparation and show most beautifully the 
mosaic arrangement of the cellular layer. On the outer side of 
the endothelial lining a framework of elastic tissue is found. 
The strongest fibres of this network are arranged in concentric 
rows in regular order, parallel with the long axis of the vein, 
while the smaller fibres take a diagonal or radiate course. In 
this elastic network are found bundles of connective tissue 
crossing each other in all directions. These fibres are very 
dense immediately beneath the endothelial layer, and are inti- 
mately interlaced with the elastic tissue; towards the periphery 
they are more loosely arranged. An elastic membrane, which 
in the arteries completely separates the endothelial from the 26 
muscular layer, does not exist in the veins. In transverse sec- 
tions of a vein, the longitudinal elastic fibres appear as light, 
round, or oval objects between the loose wavy connective-tissue 
bundles, and in the spa es surrounding them an occasional 
spindle or stellate cell with a large nucleus may be seen. 
Muscular tissue is not to be found in the superficial cutaneous 
veins of dogs. It is also absent in the internal jugular and femo- 
ral veins. The adventitia consists of loose connective tissue and 
firm elastic fibres, separated by a distinct space from the middle 
coat. 
III. Intermediate Ligature, Ligature en masse. 
All of the older surgeons were in fear of a too early separation 
of the ligature, and aimed to prevent secondary hemorrhage as 
the result of such an occurrence by including adjacent tissues, 
thus protecting the vessel against undue pressure. The object 
of this practice was simply to apply the ligature as a provisional 
mechanical agent to arrest the flow of blood in a vessel without 
any theory as to the permanent closure of the vessel. The 
ligature was passed underneath, with points of entrance and 
exit some distance from the vessel and firmly tied. This method 
was practised by Pare, and through his influence and example 
it was adopted by all of the prominent surgeons until nearly the 
end of the 18th century. Guillemeau, Thevenin, Garengeot, 
LeDran, Louis, Dionis, and Petit were faithful followers of Parc, 
and with few unimportant modifications followed his directions 
to the letter. Since the definitive closure of vessels has been 
made an object of study and experiment this method of ligation 
has been abandoned and is only resorted to in exceptional cases 
where isolation of the vessel or vessels is impossible from the 
nature or location of the wound. 
IV. Immediate or Direct Ligature. 
The experiments of Jones led the way to the immediate or 
direct ligature. Jones and his followers placed great stress on 
the laceration of the inner tissues of an artery by the circular 27 
constriction of the ligature in effecting provisional and definitive 
closure of the lumen of the vessel. The simple round ligature 
was gradually adopted by all surgeons who aimed at division of 
the internal coats by the ligature. The size of the ligature has 
also undergone considerable modification. Bell used fine oiled 
ligatures which he supposed would apply themselves accurately 
to the artery. Some united from two to as many as eight 
(Arndt) ligatures into one string. 
Lisfranc used moderately broad ligatures, but he claimed that 
in tying the knot they were changed into round cords and 
would as effectually divide the inner coats as the round ligature. 
Velpeau used ligatures proportionate in size to the vessel to be 
ligated. Hodgson used the fine round ligature. Lawrence 
spoke highly of the use of very fine silk, dentist's silk, in tying 
arteries of any size. A. Cooper also was in favor of the round 
single ligature. The circular constriction of Jones, with a single 
round thread, by degrees won the favor of surgeons and has 
firmly maintained its position as the best method of ligation 
until the advent of the aseptic ligature. The advantages pre- 
sented by this method during its pre-antiseptic period were: 
I. Effective and safe provisional closure of vessel. 2. Promotion 
of process of definitive closure of vessel. 3. It favored the 
spontaneous elimination of the ligature by diminishing the 
amount of tissue included in the loop of the ligature. 
V. Scarpa's Aplatissement. 
Scarpa's ligature was intended by its author to fulfil the two 
essential indications in obliterating the lumen of a vessel: I. 
To arrest the circulation temporarily by mechanical pressure 
without lacerating the tissues of the vessel. 2. To approximate 
and keep in constant and accurate contact a comparatively large 
surface of the inner vessel walls for union to take place by 
adhesion. His leading idea was that the intima resembles 
serous surfaces, and for rapid union to take place only a moderate 
amount of irritation is necessary, and that the injury inflicted 
by the circular ligature is too severe to obtain the most desirable 28 
result. He used ligatures two lines in width and tied over a 
small cylinder of linen. The ligature is usually expelled 
spontaneously about the fifteenth day, but if this is not the case 
and it is loose upon the vessel it should be removed at this 
time. Scarpa's theories found many admirers, who introduced 
modifications in the operation to suit their individual ideas. 
Forster substituted for the cylinder of linen, charpie and cork, 
Deschamps agaricus, Desault small plates of wood, Cline cork, 
and Roux small rolls of diachylon plaster. 
In England this practice was advocated by Crampton, and in 
France it was represented more particularly by Boyer and 
Roux. Some exponents of the' theory of aplatissement, while 
believing in the doctrine, objected to the introduction of foreign 
bodies into the wound, which they regarded not only as useless 
but injurious to the healing of the wound. Jameson used 
ligatures made of strips of raw chamois skin, which he claimed 
would by their pliability and elasticity hold in approximation 
the inner vessel walls without inflicting injury to its tissues. 
Without means to prevent suppuration it can be readily under- 
stood that the expectations held by the originator of this method 
of ligation and his followers were not realized, and it was by 
degrees displaced by the round ligature. 
VI. Double Ligature. 
The double ligature is mentioned by Celsus and zEtius, 
Rolandus of Parma speaks of the double ligature as applied 
to the vena organica (jugularis). John Bell and Maunoir not 
infrequently applied two ligatures in close proximity. In ligat- 
ing arteries in their continuity Abernethy always applied the 
double ligature after isolating the vessel freely, claiming that 
even if the intermediary isolated portion sloughs the ligatures 
will successfully guard against secondary hemorrhage. As an 
important advantage of this method he mentions that the vessel 
can be divided between the ligatures which relieves tension and 
allows both ends of the artery to retract into the tissues-occupy- 
ing then the same favorable position as vessels divided during 29 
an amputation. The double ligature has been frequently 
employed in experiments for the purpose of studying the process 
of cicatrization in bloodvessels, after ligature, and will be again 
referred to in that connection. 
According to time, ligatures may be classified into: I. Momen- 
tary; 2. Temporary; 3. Permanent. The first two varieties 
aim at obliteration of the lumen without loss of continuity of the 
vessel, while until recently the permanent ligature was always 
expected to divide the artery before it could be eliminated as a 
foreign body from the wound. 
VII. Momentary Ligature. 
A series of experiments on animals made by Jones satisfied 
him that frequently definitive closure of an artery takes place 
by drawing the ligature tightly and removing it at once. The 
rupture of the internal coats in many instances produced satis- 
factory closure by mechanically interfering with the circulation, 
and causing the formation of a thrombus, the definitive oblitera- 
tion following as the natural consequence of the traumatism. 
To insure these results more constantly, he made several of 
these circular constrictions in close proximity, so as to inflict a 
greater amount of traumatism, and procure a larger surface for 
cicatrization. Jones called attention to the superior advantages 
offered by this method of ligation over all other methods, as it 
would secure obliteration of vessels without incurring the neces- 
sity of leaving a foreign substance in the wound. Unfortu- 
nately, however, the results obtained were so uncertain that he 
did not dare to recommend its adoption in practice. In many 
instances, as late as the third or fourth day, the artery was 
found permeable, a sufficient proof that the operation with all 
its other advantages lacked reliability. 
Porta made fifty experiments with the momentary ligature on 
dogs, sheep, and goats, with the result that in only ten partial 
or complete obliteration of the vessel by thrombus or lymph- 
coagulum followed, while in all of the remaining cases only 
division of the inner coats could be demonstrated. 30 
Maunoir attempted to accomplish the same object by different 
means. He crushed the internal coats of arteries with a for- 
ceps of his own construction, and expected the same series of 
changes to occur in their interior as the result of the laceration 
of tissue, but his results must have been equally unsatisfactory, 
as the procedure does not appear to have been adopted to any 
extent in practice. 
VIII. Temporary Ligature. 
The temporary ligature was introduced for the purpose of 
obviating the deleterious effects of the presence of a foreign 
body in the healing of a wound, and the process of cicatrization 
in the bloodvessel. While the ordinary ligature remained for a 
period of time varying from three to twenty days, it has been 
argued that the average time necessary for the ligature to 
remain is much less, hence various contrivances were invented 
which were intended as substitutes for the ligature, and which 
could be removed with greater facility after the necessary time 
had elapsed, such were the pressure forceps designed by 
Deschamps, Desault, Percy, Assolini, Koehler, Porter, Billroth, 
L'Estrange, Richardson, Crampton, Nunnelly, Wolfe, Jeoffresson, 
and Speir. A similar function and sphere was assigned to the 
percutaneous acupressure of Middeldorpf, the ansa fili metallici 
of B. v. Langenbeck, the filo pressure of Dix, the ansa haemos- 
tatica a tergo of Schmitz, and more recently the amovable 
ligature of V. v. Burns. The laborious researches of Jones 
pi epared the way for the temporary ligature. Travers believed 
with Jones that vessels arc obliterated by inflammatory adhesive 
exudation and union between the inner coats, but affirmed that 
the inflammatory process requires a longer period of time to 
secure the requisite firmness in the adhesions. His first experi- 
ments were directed towards ascertaining the length of time 
required for a sufficiently firm adhesion to take place. The 
experiments were made on carotids of horses and asses. The 
ligature was applied either in the form of a loop or tied over a 
tape placed parallel with the artery for the purpose of facilitat- 31 
ing its removal. The ligature was removed after one, two, and 
six hours, and the animal killed from twenty to thirty hours 
after the operation. In fifty per cent, of the cases, where the 
ligature remained for one hour, the vessel was not obliterated. 
In all cases where it was allowed to remain from two to six 
hours, the experiment proved successful. From these experi- 
ments he concluded that six hours is the longest time required 
for the ligature to remain, and that at this time definitive occlu- 
sion has always been accomplished. 
With a view to determine whether the closure of the vessel 
is perfect at this time, or whether this is effected after the 
removal of the ligature, he made another series of experiments, 
dividing the artery on the peripheral side after removing the 
ligature. These experiments satisfied him that definitive closure 
takes place after the removal of the ligature, and is effected by 
an exudation of plastic lymph. If the ligature remained for 
twelve hours, and the artery was cut on the peripheral side, no 
hemorrhage followed its removal. He reduced his theory to 
practice by ligating the brachial artery in a man suffering from 
aneurism, and removed the ligature fifty hours after the opera- 
tion. No hemorrhage followed, and the patient recovered. He 
next tied the femoral artery for popliteal aneurism, and removed 
the ligature twenty-seven hours later. Pulsation soon returned 
below the seat of operation. The disappointment due to the 
failure in this case deterred him from giving the temporary liga- 
ture further trial, and he returned to the ordinary ligature. This 
method was tested by a few English surgeons, but, not meeting 
with more encouraging results, was soon completely abandoned. 
Scarpa, in Italy, was the next advocate of the temporary ligature. 
His pathological views regarding the use of the ligature and 
the process of obliteration of vessels, as well as his method of 
ligation, are given elsewhere. 
Delpech claimed that a few days after ligation, the ligature is 
found loose on the vessel, and consequently could exert no 
influence for good, and therefore should be removed like any 
other foreign body, so as not to interfere with the normal heal- 
ing of the wound. 32 
Velpeau also regarded the temporary ligature with favor. P. 
U. Walther studied the effects of the temporary ligature on 
animals. With a ligature-instrument of his own device, he 
aimed to divide the inner coats of the vessel, and removed the 
ligature after forty-eight to seventy-two hours, when definitive 
closure was always found perfect. 
N. R. Smith constricted the vessels with an iron wire passed 
through a silver tube, and found arteries of the fourth and fifth 
size obliterated after six hours. The femoral artery was found 
permanently closed after two days. Victor v. Bruns originated 
his method of filo-pressure in 1868.1 The silk ligature which 
he used was passed around the artery and brought out of the 
wound through a silver canula with a crossbar, to which it was 
fastened. Arteries of the size of the radial he found closed 
after eighteen hours, while larger arteries required from one to 
three days. For six years this method was used exclusively in 
all cases requiring ligation in Bruns's clinic with entire satisfac- 
tion. Only in two cases did secondary hemorrhage occur; in 
one instance the common carotid was ligated during an opera- 
tion for the removal of a cancerous tumor of the thyroid gland, 
the ligature was removed on the fifth day; in the second case 
the femoral artery was ligated, and the ligature removed on the 
third day. The great objections against the temporary ligature 
always have been, that the wound could not be completely 
closed, or had to be reopened at the time of removal of the 
ligature, thus increasing the risks of suppuration, and preventing 
primary union of the wound, circumstances which the ligature 
was intended to obviate. Absence of suppuration and primary 
union of the wound are the most reliable safeguards against 
secondary hemorrhage after any method of ligation, and any 
method which cannot secure these results with some degree of 
certainty, must be considered as faulty in principle and practice, 
and this can be said without hesitation against the temporary 
ligature as described above. The aseptic animal ligature must 
1 Paul Bruns, Die temporare Ligatur der Arterien, Deutsche Zeitschr. f. Chir., 
B. V., S. 327. 33 
be considered as a temporary ligature in every sense of the 
word, only that the material of which it is composed is re- 
moved by healthy active granulations instead of by the hand of 
the surgeon, an advantage which it would be difficult to over- 
estimate, and which neutralizes all valid objections against the 
temporary ligature. The ligature of the future, then, will be 
the aseptic animal ligature. 
IX. Permanent Ligature. 
The permanent ligature is composed of a material which will 
remain for the most part unchanged in the tissues of the body, 
and is either permanently retained (encysted) or spontaneously 
expelled. Before the aseptic ligature came into use, the ligature 
usually cut its way through the remaining tissues of the artery in 
from three to twenty days, by a process of molecular death, and 
was spontaneously expelled, thus destroying the continuity of 
the vessel in every instance. Hodgson held that the ligature 
as usually applied divides the two inner coats of the vessel, and 
destroys the vitality of the circular constricted portion of the 
adventitia, which separates like any other slough and comes 
away in the loop of the ligature. The same explanation is given 
by Guthrie, Brodie, and Gross. Bruns, however, maintains that 
the constricted portion under the pressure of the ligature under- 
goes molecular necrosis, a process necessarily attended by sup- 
puration. He also claims that in animals, if the ligature is cut 
short, it cuts through the tissues and is encysted in the cicatrix. 
Porta studied the future fate of ligatures in the wound experi- 
mentally. He made 300 experiments, using catgut, silk, hemp, 
linen, and horse-hair ligatures, cutting them short. The animals 
were killed from a few days to three years after the operation. 
Of the 300 ligatures, 64 were completely absorbed (of 80 catgut, 
33 ; of 120 silk, 19 ; of 50 linen, 10; of 40 horse-hair, 2). Of the 
236 ligatures which remained in the wound, only 26 were found 
lodged in an abscess cavity. He claimed that the ligature 
destroys the continuity of the vessel by interstitial absorption. 
P. U. Walther in his numerous experiments with the tempo- 34 
rary ligature found the adventitia divided in only one case. He 
removed the ligatures at variable periods of time (i hr.-i lohrs.) 
after operation. P. Bruns1 made fifteen experiments to deter- 
mine the effect of the ligature on the coats of vessels, and con- 
firmed the observations of Walther. If the constricted portion 
of an artery is examined some time after the application of the 
ligature, it is not always easy to determine whether complete 
division has taken place or not. A few days after ligation the 
artery in close proximity to the ligature is thickened, the 
swelling on each side effacing the depression made by the 
ligature, and shutting the ligature out of sight. The traumatic 
peri-arteritis produces a connective-tissue proliferation which 
covers the ligature and both ends of the artery in a similar 
manner as the provisional callus after fracture surrounds the 
broken ends of the bone. If the inflammation does not proceed 
beyond the process of tissue formation, the granulation tissue is 
converted into cicatricial tissue, which forms an additional con- 
necting medium between the ends of the artery, and by forming 
at the same time a capsule around the ligature, the latter becomes 
permanently encysted. If the end of an artery is tied, the vi- 
tality of the ligated stump will depend on the manner in which the 
wound heals ; if suppuration takes place it will in all probability 
separate as a slough, and with the ligature will escape with the 
wound secretions ; if, on the other hand, the wound heals by pri- 
mary union it will either remain in organic connection with the 
vessel and form new vascular communications with the adjacent 
tissue, or in the event of a cutting through of the ligature it may 
still retain its vitality and remain in the tissues, or finally it may 
be removed by gradual absorption. John Bell and Otto Weber 
were convinced that the end of the ligated vessel invariably 
separates and dies. There is, however, good reason to believe 
that the ligated artery stump in the absence of suppuration will 
retain its vitality and will again unite with the surrounding 
tissues from which it receives its nutrition. P. Bruns made a 
few experiments in this direction. 
1 Op. cit. 35 
Experiment No. i.-Double ligation of carotid artery of a dog ; 
division of artery between ligatures. The animal was killed, and 
parts were examined fourteen days after operation. The ends of 
the artery were separated 2 ctm., the interspace was bridged over 
by a band of connective tissue in which were embedded both ligated 
stumps a short distance from the closed ends of the artery. 
Experiment No. 2.-Vessels and operation the same. The 
separated ends of the artery embedded in the intermediate con- 
nective-tissue string. 
Experiment No. 3.-Femoral artery, operation the same. Local 
conditions the same, only that the bridge of new connective tissue 
was larger and firmer. The separated ends of the artery somewhat 
reduced in size. 
Experiment No. 4.-Femoral artery, operation the same. Sepa- 
rated pieces much smaller, and incorporated in the newly formed 
connective tissues. 
In all of these experiments it appears that the ligature cut its 
way through the tissues of the artery, thus completely separating 
the ligated stumps, and still they retained their vitality through 
the influence of the surrounding living tissue. The ligatures 
were undoubtedly drawn very tight, and as the operations were 
done without antiseptic precautions the reaction was in excess 
of what is necessary to obtain obliteration of the vessels, and 
these circumstances will go far towards furnishing an explanation 
of the uniformity with which the constricted portion of the vessel 
gave way under the ligature. The use of the aseptic ligature 
and antiseptic wound treatment tend to preserve the continuity 
of the ligated vessel, as has been abundantly proved by clinical 
experience and experimental research. In many of my speci- 
mens it can be seen that weeks and months after the operation 
the ligatures remained in their original location and occupied 
the same relative position to the vessel as immediately after the 
operation, the ligature in every instance where suppuration was 
prevented being surrounded or encapsuled by a dense capsule 36 
of connective tissue. If under antiseptic precautions the end of 
an artery is ligated, the stump of the artery retains its vitality 
in a similar way, and is nourished in the same manner as the 
pedicle after ovariotomy, with the only difference that in the 
former instance the local conditions are perhaps more favorable 
for the preservation of the vitality of the ligated parts. 
X. Aseptic Ligature. 
In his first communication to the profession on this subject 
Lister alludes to the advantages of the aseptic ligature as fol- 
lows: "If the antiseptic ligature be employed it merely inflicts 
a wound or injury upon the vessel, without introducing any 
permanent cause of irritation. The injured part, therefore, 
becomes repaired after the manner of a subcutaneous wound 
without passing through the process of granulation and suppura- 
tion, which is induced by the employment of the ordinary sep- 
tic ligature."1 It may now be truly said that some form of asep- 
tic ligature is used at present by almost every surgeon, and that, 
while the merits of the antiseptic, treatment of wounds are still 
denied by many, few or none would dare to use the ordinary 
ligature without realizing that their duty towards their patients 
had not been conscientiously discharged. Perhaps no other 
surgical procedure has ever enjoyed the confidence of the whole 
profession throughout the civilized world to the same extent as 
the aseptic ligature. This universal faith in the reliability and 
safety of the aseptic ligature is only a natural outgrowth of the 
superior results following its use. Protracted suppuration in 
wounds, the result of retained ligatures, secondary hemorrhage, 
and suppurative inflammation of vessels have been gradually 
diminishing in frequency, and bid fair under the influence of the 
aseptic ligatures to be almost completely expunged from the 
future category of wound complications. Nussbaum very ap- 
propriately remarks: " Catgut is without doubt Lister's greatest 
discovery."2 And again: "How pleasant it is to cut the liga- 
1 London Lancet, April 3, 1869. 
2 Leitfaden zur antiseptischen Wund-behan dIung. Stuttgart, 1879,8. 23. 37 
tures short and leave them unconcerned to their fate in the 
wound! In ovariotomies, etc., their value cannot be overesti- 
mated. The manner in which catgut adheres to an artery, form- 
ing connections with it and the surrounding tissues, assisting at 
the same time in forming a firm ring around the coats of the 
artery, are exceedingly welcome occurrences, guarding against 
secondary arterial hemorrhage in ligating in the continuity of a 
vessel, and rendering even the application of a ligature in close 
proximity to a large collateral branch devoid of danger. All 
this silk cannot do." Before the introduction of antiseptic sur- 
gery suppuration at the seat of ligature was almost a necessity. 
As suppuration interfered seriously with the hyperplastic pro- 
cesses in the tissues of the arterial tunics, secondary hemor- 
rhage was of frequent occurrence, because the adhesion between 
the surfaces of the interior of the vessel walls were not suffi- 
ciently firm to resist the intra-arterial pressure at the time of the 
separation of the ligature. It was on this account deemed 
necessary by the older surgeons in deligating an artery in its 
continuity to apply the ligature at least an inch distant from the 
next collateral branch so as to favor the formation of a thrombus. 
The aseptic ligature marks a new era in the surgery of blood- 
vessels. Ligating a vessel under antiseptic precautions presents 
the following advantages:- 
I. The ligature remains undisturbed in the wound, becoming 
either absorbed or encysted after having fulfilled the purpose of 
a provisional haemostatic. 
2. Prompt obliteration of the vessel takes place by prolifera- 
tion of new tissue elements from pre-existing cells independ- 
ently of the formation of a thrombus, in fact thrombosis is often 
wanting. The constricted portion of the vessel does not necrose, 
it is infiltrated like the catgut with living tissue.1 Bardeleben 
makes a similar assertion.2 
In all operations with the aseptic ligature the small size of 
the clot and its frequent entire absence is in remarkable contrast 
1 C. Hueter, Grundriss der Chirurgie, 1880, B. I. p. 146. 
2 Berl. klin. Wochenschrift, 1875, No. 29. 38 
with the results observed after the ordinary septic ligature. The 
importance of the thrombus as an active agent in the definitive 
closure of vessels has vanished before the brilliant results ob- 
tained with the aseptic ligature. John A. Lidell, in speaking of 
vein ligature, says: "If a ligature of animal origin, such as 
carbolized catgut, has been applied the approximated walls grow 
directly together, and the ligature itself disappears by absorption 
or is replaced by new connective tissue."1 
A discrepancy of opinion still exists regarding the time in 
which the catgut ligature is absorbed. The results of experi- 
ments in this direction have not been uniform. Lister ligated 
the carotid artery of a calf with carbolized catgut, and on exam- 
ining the parts, thirty days after operation, he found only small 
portions of the ligature remaining, the rest absorbed and its 
space occupied by new tissue. 
Czerny operated on rabbits, and examined the parts from one 
to thirty days after operation. After a number of days the liga- 
ture was always found loose on the vessel, softened and infil- 
trated with cells. Fillenbaum applied a double ligature to the 
carotid artery of a dog, and killing the animal fourteen days 
subsequently found only microscopical remnants of the ligatures. 
Schurhardt experimented with guinea pigs, and if the ligature 
was allowed to remain for five weeks, only traces of it remained. 
P. Bruns2 operated on dogs four times, tying the femoral and 
axillary arteries, no antiseptic precautions being used, and the 
specimens were examined after ten days. In two cases catgut 
ligatures had undergone but little change; in the third case the 
ligature could not be detected with the naked eye, but the 
microscope showed traces of it; in the fourth case a double liga- 
ture had been applied to the femoral artery four ctm. apart, and 
in this instance the proximal ligature showed no change, while 
of the distal ligature only the knot remained. He also ligated 
the carotid artery three times and examined specimens after 
twenty days had elapsed, and found only in one instance traces 
1 Injuries of Bloodvessels. The Intern. Encycl. of Surgery, vol. iii. p. 211. 
2 Die temporiire Ligatur der Arterien, Deutsche Zeitschr. f. Chirurgie, B. V. 39 
of the ligature on making longitudinal section of the vessel. 
In two cases he examined the ligatures after thirty days, the 
carotid and axillary arteries being the vessels tied, and found 
only microscopical traces. In four more operations he tied the 
axillary and femoral arteries, and examined after forty days, and 
on careful examination found traces of the ligature only in one 
case, while in the remaining three the microscope revealed only 
traces. From these experiments he concluded that the catgut 
ligature from the first to the tenth day is either not changed at 
all, or that the changes are not constant; absorption is constant 
from the twentieth to thirtieth day, and after the fortieth day 
only microscopical remnants can be found. 
M. Arnaud, in a series of careful experiments, gives these 
results in regard to the absorption of carbolized catgut liga- 
tures :-1 
Catgut disappeared once in ..... 4 days 
" " twice in . . . . . 7 " 
" " once in . . . . . 9 " 
Catgut distinctly visible once in . . . . 4 " 
.... 9 " 
tt tc cc cc J j (( 
Catgut visible but softened and infiltrated once in . 16 " 
The time required for absorption, although variable in the 
same animals and in the same locality, will depend on : 1. The 
quality of the ligature ; 2. The size of the ligature ; 3. The nature 
of the tissue with which it is kept in contact; 4. The presence 
or absence of suppuration. P. Bruns claims that catgut is dis- 
solved by pus, hence it will disappear in a shorter time in 
wounds that suppurate. In my experience I have observed the 
contrary. In suppurating wounds I have seen the catgut remain 
unchanged for an exceedingly long time, and after weeks have 
seen the ligature come away in the secretions, having under- 
gone but little change. The absorption of the catgut ligature 
is accomplished by a process of softening and infiltration of 
cellular elements, and is consequently accomplished in the 
1 Richard Barwell, Aneurism, Encycl. of Surgery, New York, vol. iii. p. 442. 40 
shortest space of time, in wounds where the process of granu- 
lation is not impaired by suppuration. 
The immediate and remote effects of the catgut ligature on 
the vessel also deserves consideration. The impression prevailed 
at one time, that the catgut ligature does not destroy the con- 
tinuity of the artery. This assertion has, however, met with 
opposition. 
P. Bruns,1 in his experimental work, has made special search 
in this direction in 13 ligations of arteries in their continuity. 
In the three specimens obtained ten days after operation, he 
found the artery completely severed in one instance, while in 
the other two cases a fine thread of adventitial tissue was found 
in the loops of the ligatures. In the remaining ten cases, where 
only traces and microscopical remnants of the ligatures could 
be found, three different conditions of things presented them- 
selves. In three cases the vessel was completely divided in the 
same manner as after using the ordinary ligature, only the inter- 
mediate space between the vessel ends was less than after using 
the silk ligature, the space measured only from i| to 3 mm., and 
was filled in with connective tissue. In six cases a solution of 
continuity had apparently not taken place, and its existence was 
ascertained only by close examination. The place of ligature 
presented a somewhat prominent circular ring; on making a 
longitudinal section, the intima and media were found severed, 
and their margins directed towards the interior of the vessel, 
shutting off its lumen on both sides by a concave or funnel- 
shaped end. The interspaces between both blunt ends was 
occupied by a solid intermediary substance about the thickness 
of the ligature and continuous with the adventitia. The inter- 
mediary substance was composed of young connective tissue 
interspersed with particles of the catgut ligature. In one case 
the continuity of the vessel was perfect, all of its coats being 
entire. Evidently the ligature was not tied with the same degree 
of firmness as in the other cases. The lumen was only nar- 
rowed by the ligature and rendered impermeable by a thrombus. 
* Op. cit. 41 
Bruns is willing to admit, that in case the catgut ligature is 
drawn only sufficiently tight to interrupt the circulation, all of 
the coats of the artery remain intact during the healing process, 
and the continuity of the vessel is preserved in the strictest sense 
of the word. In the cases where division of the vessel took 
place, and a bridge of connective tissue, corresponding to the 
diameter of the ligature, formed, he also asserts that practically 
this process may be regarded as similar to the process of heal- 
ing without loss of continuity of the vessel-tunics. 
Stimson1 agrees with Bryant, that the catgut ligature not only 
primarily divides the twro inner coats of an artery like the ordi- 
nary silk ligature, but that subsequently the adventitia also gives 
way under the pressure of the ligature, thus completely inter- 
rupting the continuity of the vessel. They affirm that the bridge 
of intermediary connective tissue may impart an appearance as 
though no division had occurred. The results of my experi- 
ments have demonstrated to my satisfaction that it is not neces- 
sary to tie with sufficient firmness to divide any of the arterial 
coats, and yet prompt obliteration of the artery will ensue, and 
that in such instances the coats of the vessel are transformed into 
a solid string of connective tissue, the best possible result which 
.can be obtained after ligature. Even in case the ligature is tied 
with sufficient force to rupture the inner coats, the constricted 
adventitia may retain its vitality, and form a part and parcel of 
the intermediary connective tissue uniting the two ends of the 
vessel; and still further, if the vitality of the adventitial coat is 
suspended, and it is removed by a slow process of molecular 
disintegration and absorption, it is replaced by tissue elements 
which are converted into a similar tissue, thus practically pre- 
serving the continuity of the vessel. In the event of suppura- 
tion, the advantages of the aseptic catgut ligature are lost, and 
the ligature escapes with the discharges either entire and un- 
changed, or in fragments after it has undergone softening and 
disintegration. Ligatures made of any other animal tissue 
rendered properly aseptic are disposed of in the wound in a 
1 The Antiseptic Catgut Ligature, Amer. Journ. Med. Sciences, 1881, p. 131. 42 
similar manner as catgut, and it has not been proved that any 
of them possess any advantages over the well-prepared catgut 
ligature. 
Mr. Barwell,1 in tying large arteries, uses a broad ligature 
made of the strong middle coat of the ox's aorta. His idea is 
to approximate the intima without rupturing it. In sixteen cases 
of ligation of large vessels it proved successful. In one case of 
ligation of the femoral artery, hemorrhage occurred from a 
small vessel near the ligature at the time of operation; at the 
request of Mr. Barwell, two more ligatures were applied within 
an inch of the first ligature, and the case terminated favorably. 
Mr. Barwell still maintains the novel belief that his ligature 
material is not absorbed, but is organized and becomes a part of 
the living tissue around it. Aseptic ligatures made of materials 
which are not capable of being absorbed remain in the wound 
and are encysted. All of these ligatures are more prone to 
destroy the continuity of the vessels than animal ligatures, but 
they do not do so invariably. Czerny's silk, for example, which 
is used next in frequency to catgut, is infiltrated with cellular 
elements, and, after a long time, is partly absorbed and com- 
pletely encysted. 
XI. Thrombosis after Ligature. 
One of the most serious objections against the prevalent 
doctrine of obliteration of vessels through the instrumentality 
of an organized thrombus, is the fact that, in many instances, 
coagulation of the blood fails to take place after tying a vessel 
with a ligature, and that primary union of its inner walls has been 
frequently demonstrated without thrombus formation. The 
conditions which determine intravascular coagulation after liga- 
ture are still not well known. Alexander Schmidt has shown 
that fibrin as such does not exist in blood, but that it is the 
product of a union between two substances, the fibrinogen and 
paraglobin, under the influence of a fibrin ferment, and he has 
1 International Encylopaedia of Surgery, New York, vol. iii. 43 
further shown that fibrinogen is contained in the plasma of the 
blood in solution, and that the fibrinferment and paraglobin are a 
product of the white corpuscles of the blood. Only after disso- 
lution of the white corpuscles are paraglobin and fibrinferment 
set free, and can act on fibrinogen. Consequently, as long as 
the integrity of the white blood-cells is preserved, coagulation 
cannot take place. As fibrin does not pre-exist in the blood, 
it is the product of chemico-vital changes which take place 
before and during the process of coagulation. During coagu- 
lation the vitality of the morphological elements in the thrombus 
is lost as the white blood-corpuscles lose their identity, and their 
protoplasm unites with the fibrinogen contained in the serum and 
produces the fibrin. The endothelia lining the intima as long 
as they retain their vitality prevent the spontaneous death of 
the white blood-corpuscles, and this prevents the formation of 
fibrin. 
Virchow attributed coagulation to the diminished motion or 
arrest of the current of blood in the vessel, but this cause has 
been found insufficient in itself to produce a thrombus provided 
the endothelia retained their normal qualities. Baumgarten has 
shown that a column of blood can be kept in a fluid condition 
for weeks within a vessel between two aseptic ligatures. If after 
several weeks the blood was allowed to escape through an in- 
cision in the-tied portion of the vessel it coagulated the same as 
blood drawn from any other locality, showing that it had not 
lost its coagulating properties by its long confinement between 
the ligatures. This interesting phenomenon can only be ex- 
plained by assuming that the aseptic ligature preserves the 
vitality even of the torn inner coats which successfully prevents 
loss of vitality of any of the white blood-cells. Some twenty 
years ago the famous experiments of Bruecke demonstrated 
that living tissues resist coagulation, and Baumgarten's experi- 
ments certainly most beautifully substantiate this assertion. It 
is a well-known fact that coagulation takes place with the 
greatest degree of certainty and becomes more extensive in pro- 
portion to the magnitude of the traumatism inflicted by the 44 
ligature and the degree and extent of the subsequent inflamma- 
tion. 
Until recently the universal belief prevailed that foreign sub- 
stances introduced into the circulation invariably produce coagu- 
lation. This doctrine has also been successfully refuted. Zahn's 
investigations have demonstrated beyond all possible doubt that 
coagulation only follows the introduction of substances which 
have not been properly disinfected. He introduced aseptic 
pieces of glass and rubber, and never observed coagulation fol- 
lowing this procedure. 
Hueter, in speaking of thrombosis in veins, refers to our sub- 
ject as follows: "Whether by following antiseptic precautions 
the formation of a thrombus can be prevented with the same 
degree of certainty as in the case of arteries remains an open 
question. It is certain, however, that septic infections favor 
coagulation in veins."1 Of this latter assertion clinical experience 
furnishes abundant proof. It is more than probable that during 
the progress of many of the infectious diseases, many of the lin- 
ing endothelia of the intima are destroyed, and that the white 
corpuscles coming in contact with dead tissue lose their vitality 
and produce thrombosis. But even under the old pre-antiseptic 
treatment thrombus formation was by no means a constant re- 
sult after ligation. Walther, in 28 experiments to determine 
this question, found a thrombus in both ends of the vessel 18 
times. In one case there was no thrombus on either side of the 
ligature, and in one only on the cardiac side, while in the re- 
maining 8 cases the thrombus was found only in the distal end 
of the artery. 
Porta has made the largest number of experiments to ascer- 
tain the relative frequency of thrombus formation after ligature. 
In 250 cases of ligation of large arteries in animals in which the 
vessels were examined for this purpose, he found in 35 cases no 
traces of a thrombus, and yet he observed only 3 cases of sec- 
ondary hemorrhage after 400 ligations. 
Schumann2 made 54 experiments on dogs and rabbits with a 
1 Grundriss der Chirurgie, 1880, vol. i. p. 148. 
2 Virchow u. Hirsch's Jahresb. 1874, vol. ii. p. 377. 45 
view to study the provisional and definitive closure of vessels 
after ligature. Thrombus formation had only occurred in 32 
per cent, of the cases, and the coagulum in all of these cases 
was usually small. It is evident from these statistics that 
thrombus formation after ligature frequently fails to take place, 
and that in this event closure of the vessel is effected by tissue 
proliferation from the vessel tunics. It would hardly appear 
reasonable to assume with Kocher, that in these cases a 
thrombus so minute in size as to elude detection by the naked 
eye might still exist, and perform the difficult task of obliterat- 
ing the lumen of the vessel. 
XII. Organization of Thrombus. 
By organization of a thrombus we understand that some of 
its morphological elements retain their vitality and power of 
tissue proliferation. In this sense the term is used by all authors 
who have attributed to fibrin, white blood-corpuscles and red 
blood-corpuscles the property of being converted into connec- 
tive tissue. If the intra-vascular thrombus possesses this quality, 
it is certainly an exception to the general rule, as extravasations 
of blood in any other locality of the body are never known to 
undergo organization. Under the most favorable circumstances 
they are destined to succumb to retrograde metamorphosis leav- 
ing eventually nothing but haematoidin crystals as landmarks of 
their former existence. 
Serous membranes afford a favorable surface for rapid absorp- 
tion of blood, so much so that the peritoneal cavity has been 
utilized for the purpose of performing transfusion of blood. 
Copious effusions of blood into joints are usually promptly 
absorbed, leaving no permanent ill results as far as the functions 
of the joints are concerned. Immense extravasations into the 
cellular tissue about the seat of fractures, or the result of other 
injuries, are completely absorbed in a remarkably short time, 
provided suppuration is prevented. The anterior chamber of 
the eye, from the peculiar anatomical structure of its walls, is 
an exceedingly favorable locality for successful tissue transplan- 46 
tation, as has been demonstrated by Dorremal and Goldzieher, 
and yet every oculist can testify to the fact that extravasations 
of blood in this locality never undergo organization, but are 
usually promptly removed by absorption. As an additional 
factor, it may also be mentioned that the intra-vascular thrombus 
is located disadvantageously as far as organization is concerned, 
the intima and media separating it from the nearest vascular 
supply. The assertion made by Lister that bloodclots in wounds 
under the antiseptic treatment become organized, certainly does 
not correspond with facts. If bloodclots in the interior of the 
tissues of the body, safely protected from any possible source of 
infection, invariably disappear by absorption, there is no good 
reason to believe that they will undergo any other changes when 
located in wounds. The clot itself is not organized, but simply 
serves the useful purpose of furnishing a favorable soil for the 
lodgement and propagation of new tissue-elements from the 
adjacent wound surfaces. In this sense the organization of the 
clot is accepted by Volkmann.1 He believes that the blood clot 
between the broken ends of the bone in compound fractures 
serves primarily the purpose of a soft cement substance which, 
under the protection of antiseptic precautions, is gradually dis- 
placed by substitution, and its space occupied by permanent 
tissue. 
XIII. Formation of Cicatrix in Bloodvessels after Ligature. 
The ligature fulfils a twofold object: I. It constitutes the 
most scientific and reliable provisional haemostatic, interrupting 
at once the physiological function of the vessel at the point of 
application. 2. It brings the vessel walls in mutual contact, 
and, by maintaining uninterrupted apposition for a sufficient 
length of time, it induces an active tissue proliferation which is 
destined to produce definitive obliteration of the lumen of the 
vessel. The immediate effect of the ligature in arresting the 
1 Die Behandlung der complicirten Fracturen. Volkmann's Sammlung klin 
Vortraege. No. 134. 47 
circulation was well known even to those who first resorted to 
its use, but the secondary changes, the definitive closure of 
vessels by cicatrization, has been a subject concerning which 
there has prevailed the greatest diversity of opinion and which 
still remains a prolific object for study and investigation. The 
researches of Jones laid the foundation for an intelligent and 
rational study of the process of cicatrization in bloodvessels 
after ligature. Various theories have been advanced which 
were intended to furnish an explanation of the process of 
obliteration, or to point out the particular tissue which supplies 
the material for the cicatrix. The production - of cicatricial 
tissue within the bloodvessels has been attributed to: I. 
Adhesive inflammation and plastic exudation at the seat of 
ligature without reference to any histological changes. 2. 
Fibrin. 3. White blood-corpuscles. 4. Red blood-corpuscles. 
5. Immigration corpuscles. 6. Connective tissue. 7- Endo- 
thelia. 
XIV. Formation of Cicatrix by Adhesive or Plastic Inflammation. 
The existence of adhesive inflammation has always been 
recognized as an important element in effecting permanent 
closure of a vessel after ligature. Under this head will be men- 
tioned the pathological views of older writers who studied the 
process of cicatrization independently of any accurate histologi- 
cal knowledge. 
Celsus believed that the definitive obliteration of the vessel 
was due to retraction of the artery and tumefaction of the con- 
nective tissue around it. Galen asserted that permanent closure 
takes place by a cicatrix which closes the wound in the vessel, 
believing that the arterial walls unite only in exceptional cases. 
Ponteau regarded the inflamed para-vascular tissue as the most 
important element in the obliterating process. John and Ben- 
jamin Bell believed that an artery is occluded by a plastic 
exudation which takes place from its inner walls and the 
divided ends. Scarpa, who compared the tunica intima with 
serous membranes, and attributed to it the same tendency to 48 
assume inflammatory changes and form speedy and firm adhe- 
sions, commits himself on this subject as follows:' "The 
union of the two opposite sides of an artery, as I have mentioned 
several times, only takes place by means of the adhesive inflam- 
mation, to excite which, and in order that it may produce the 
desired effect, it is necessary that the artery be not insulated too 
much, or beyond the limits of the ligature; that the degree of 
pressure be such as to put and keep the two opposite sides of it 
in complete and firm contact, that the irritation caused by the 
pressure be sufficient to produce inflammation in the proper 
coats of the artery without their passing immediately into a 
state of mortification from a want of vitality. If this degree of 
pressure be too small, the artery does not inflame sufficiently 
and is not obliterated, but is rather wasted slowly and then 
bursts; if the pressure be too great, and especially upon an 
artery insulated in a greater space than is requisite for the 
ligature, it mortifies, ulcerates, and opens before the sides of it 
have adhered to each other, both at the place of ligation and 
for a certain space above and below it." 
Porta placed great stress on the importance of primary union 
of the wound, and the appearance of an external plastic ring at 
the seat of the ligature, in securing permanent occlusion of a 
vessel. He also pointed out how suppuration would interfere 
in obtaining the most favorable results after ligation. Jones 
and Travers almost ignored the importance of the thrombus in 
effecting closure of a vessel, and assigned to the traumatic 
inflammatory exudation almost exclusively the function in 
accomplishing this object. They claimed that the ligature acts 
as an irritant to the walls of the vessel, plastic exudation taking 
place into its lumen, the torn intima and media becoming ad- 
herent, thus permanently closing the canal. 
Kirkland and White maintained that the coats of arteries near 
the ligature unite by plastic lymph, and that the coagulum is 
not only useless but may prove detrimental by interfering with 
such union. 
1 A Treatise on the Anatomy, Pathology, and Treatment of Aneurism, trans, by 
Henry Wishart, 1808, p. 277. 49 
After Virchow in his researches on thrombosis and embolism 
had demonstrated that the intima is not susceptible of inflam- 
mation, pathologists again turned their attention to the import- 
ance of the thrombus as an active agent in the process of cica- 
trization. Rokitansky,1 in opposition to Virchow, again claimed 
that the final obliteration of an artery can take place without a 
thrombus in a similar manner as in the vessels of the umbilical 
cord and the ductus Botalli. 
Ph. Von Walther2 says that the tunics of injured arteries 
inflame in a similar manner as other wounded organs. The 
phlogistic exudation takes place first in the external coat, some- 
what later in the middle coat, and latest on the free surface of 
the internal tunic. 
Cruveilhier, Castleman, and Foerster also ignored the import- 
ance of the thrombus, and pointed to the tissues of the vessel- 
walls as the active agents in the obliterating process. All of 
the authorities who mention adhesive inflammation as the 
means by which vessels are permanently closed, assign to the 
thrombus only an unimportant or entirely passive role, but at 
the same time they do not point out the particular tissue ele- 
ment which is supposed to furnish the material for the cicatrix. 
Later researches have aimed to limit the process to some special 
structure and to study and demonstrate the minute processes 
by which obliteration is accomplished. In one of our recent 
American text-books on surgery, the process of obliteration in 
an artery is described as follows: "The permanent closure and 
final and complete obliteration of these vessels (arteries) is 
effected by their continued contraction, by the effusion of fibrin 
within and around the vessels, and at length by the conversion 
of all their coats into simple cords of connective tissue. Even 
these latter may in the course of time disappear."3 
1 Handbuch der Speciellen pathologischen Anatomie. Wien, 1844, p. 616. 
2 System der Chirurgie. Carlsruhe u. Freiburg, 1843, B. i. p. 253. 
3 Hamilton, The Principles and Practice of Surgery, 1879, p. 176. 50 
XV. Formation of Cicatrix from Fibrin. 
All pathologists who ascribe to any of the pre-existing mor- 
phological elements of the thrombus the active part in the 
process of cicatrization, as a matter of necessity consider the 
presence of the thrombus essential in the process of oblitera- 
tion. 
John Hunter maintained that the fibrin in the clot is capable 
of undergoing organization, and is the active agent in producing 
permanent closure of a vessel after ligation. He based his as- 
sertion on the examination of a thrombus taken from a crural 
artery which he injected from the lumen of the vessel and found 
that it contained a network of vessels. To satisfy himself that 
organization of the thrombus takes place, he applied a double 
ligature to the carotid artery of a dog, and on examination of 
the specimen some time afterward he verified his conclusion. 
Gendrin, who repeated the experiments of Hunter, says: "If a 
quantity of blood is included between two ligatures in an artery 
or vein, it coagulates, and, as is well known, the serum is 
absorbed and a slight inflammation takes place in the walls of 
the vessel. The different parts of the thrombus are decolorized, 
a thin layer of coagulated lymph diffuses itself over the inner 
walls of the vessels which effects adhesion between thrombus 
and vessel-walls, the thrombus finally undergoes organization 
and cicatrization." 
Andral supposed that he had demonstrated in a satisfactory 
manner that fibrin in cases of pleuritic exudations and pseudo- 
membranes is converted into connective tissue, and his teachings 
were generally accepted. Henle also claimed that fibrin is 
converted into connective tissue, and that it constituted the most 
important element of the thrombus. Zwicky, a pupil of Henle, 
was the first to give an accurate microscopical description of the 
appearances in vessels after ligation. In accordance with the 
views of his preceptor, he asserted that the blood corpuscles 
only play a passive part in the process of organization of the 
clot. 51 
As late as 1872, Billroth writes: "Coagulated fibrin may, 
by aid of cells, be transformed into connective-tissue inter-cellu- 
lar substance, although I cannot decide whether this be due to 
a true metamorphosis, or to a gradual substitution of cell proto- 
plasms for disappearing fibrin."1 
It is almost unnecessary to say that at the present time no 
one can be found who claims that fibrin is capable of being 
transformed into connective tissue, but that wherever found it 
invariably disappears after a time by molecular disintegration 
and absorption. Physiology teaches us that fibrin does not 
pre-exist in living blood, but that it is formed as the result of 
chcmico-vital changes during coagulation, hence we would 
a priori conclude that such a substance is not capable of being 
elaborated into tissue endowed with a higher degree of vitality. 
XVI. Formation of Cicatrix from White Blood-Corpuscles. 
After Virchow had shown that adhesive inflammation of the 
intima is incompatible with its structure, pathologists again 
turned their attention to the thrombus as the active medium of 
the process of obliteration. The organization of the thrombus now 
became a favorite study. Stilling and Zwicky not only claimed 
that the thrombus undergoes organization, but they were also 
among the first to describe avascular network in the thrombus; 
the vessels, according to their observations, communicating with 
and originating from the lumen of the vessel. Virchow, Bill- 
roth, and O. Weber referred the organization of the thrombus 
to the presence in it of the white blood-corpuscles. Czernay 
and Schuman attributed it to the same cause. They traced 
step by step the part taken by these corpuscles in the process 
of organization of the clot. Pirogoff, Thierfelder, Gerstacker, 
and Boner, studying the fate of the white blood-corpuscles in 
subcutaneous tenotomies, found them capable of transformation 
into new connective tissue. 
i General Surgical Pathology and Therapeutics, trans, by C. E. Hackley, New 
York, 1872. 52 
The conclusions at which O. Weber arrived may be sum- 
marized as follows:- 
1. The red blood-corpuscles and fibrin of the clot disintegrate 
and disappear by absorption. 
2. The colorless blood-corpuscles in the clot, a few hours after 
the application of the ligature, enter into a transformation into 
spindle-shaped cells. 
3. After a few days the projections thrown out by these cells 
may be seen to unite with each other, and, by arranging them- 
selves in rows, plainly assume the shape of new vessels. 
4. The youngest vessels are formed in the peripheral portion 
of the clot. 
5. During the third and fourth weeks the vascularization of 
he thrombus is completed, the vessel having formed anasto- 
moses with the vasa vasorum of the adventitia. At the point 
of ligature where the intima and media have been lacerated, the 
vessels of the adventitia enter the thrombus directly; further 
from the ligature they penetrate through the two inner coats 
and enter the thrombus. 
6. About the fiftieth to the sixtieth day the thrombus is 
traversed everywhere by vessels, more especially at the peri- 
phery. A large vessel is often found in the centre of the clot. 
7. During the process of cicatrization, the vessels in the 
thrombus disappear, the lumen of the vessel becomes narrower, 
and is finally completely obliterated. 
8. The cicatricial tissue is the exclusive product of the white 
blood-corpuscles. 
9. The white blood-corpuscles multiply very rapidly by seg- 
mentation. 
10. The endothelia of the new bloodvessels in the thrombus 
are produced exclusively from the white blood-corpuscles.1 
Kocher2 has studied the organization and vascularization of 
the thrombus after ligature, and sustains the views entertained 
1 V. Pitha u. Billroth's Chirurgie, i. I. 
2 Ueber die feineren Vorgange bei der Blutstillungdurch Acupressur, Ligatur und 
Torsion, Archiv f. KI. Chirurgie, B. xi. S. 660. 53 
by Weber. He injected the vessels from the lumen of the 
artery, and examined transverse sections under the microscope. 
I will give the description of one of his specimens: On 
December 24, 1867, he ligated the right carotid artery of a dog, 
and dusted finely powdered cinnabar over the exposed portion 
of the vessel to indicate subsequently the exact location of the 
ligature. The animal was killed January 11, 1868. The opera- 
tion wound was healed. The vessel was injected with gelatine 
stained with Berlin blue, and hardened at first in a solution of 
chromate of potassa, and subsequently in alcohol; after it was 
sufficiently hardened it was thoroughly dried and inclosed in a 
coating of paraffin for the purpose of making microscopical 
sections. The decolorization of the thrombus was more com- 
plete near the ligature than towards the free lumen of the vessel. 
The proximal end of the thrombus was adherent only to one 
side of the vessel, so that the injection material penetrated the 
other side between vessel-wall and thrombus. From the free 
surface of the central end of the thrombus a central vessel of 
considerable size was seen to enter the thrombus; from it smaller 
vessels branched off and penetrated the thrombus in different 
directions, forming a beautiful network of capillary vessels, which 
left no doubt in his mind that the channels were real blood- 
vessels and not an artificial product. Wherever the thrombus 
was adherent to the intima, the latter showed small vessels from 
the adventitia, while the free surfaces of the intima remained 
non-vascular. Nearer the ligature the vascular network from 
the adventitia was more fully developed, supplying numerous 
branches to the inner coats of the artery. The torn intima at 
the seat of ligature was arranged in folds, its free and irregular 
margins sending prolongations into the thrombus. The media 
was also divided by the ligature, so that the thrombus pene- 
trated between its fibres. While the vascularity of the vessel- 
wall increased towards the ligature, the vessels in the thrombus 
became smaller in the same ratio, to disappear completely near 
the ligature. These appearances satisfied him that the vascular 
supply of the thrombus is derived directly from the free lumen 
of the vessel, while the vasa vasorum increase in size and num- 54 
ber, and distribute branches to the inner tunics over an area 
corresponding with the adherent portions of the thrombus. He 
agrees with O. Weber that canalization of the thrombus initiates 
organization. He also made a number of experiments where 
the conditions for thrombus formation were exceedingly unfavor- 
able, by tying arteries in close proximity to a large collateral 
branch, in all cases where the experiment proved successful, 
he found the two inner tunics ruptured, and in every instance 
no direct union of the lacerated tissues, but cicatrization was 
always the result of a thrombus, which in some instances was 
exceedingly small, almost microscopical in size. For the pur- 
pose of proving that the tissues of the arterial coats take no 
active part in the process of obliteration, he made the following 
experiment: The right carotid artery of a dog was tied Decem- 
ber 24, 1867, in two places, 2 ctm. apart, the blood in the inter- 
mediate space having been squeezed out between two fingers 
before tying the peripheral ligature. Cinnabar was dusted over 
the vessel in the wound. The animal was killed January 11, 
1868. The wound was healed. The vessel on the cardiac side 
was closed by art extensive adherent thrombus. Between the 
ligatures the vessels contained a very small adherent thrombus, 
the greater portion of the lumen being empty. Transverse 
section through this portion of the artery revealed the star- 
shaped lumen of the vessel, the folds of the intima being in 
contact but not acherent. No proliferation of the vessel-wall 
or the epithelium could be observed. The staining material was 
found diffused in the para-vascular connective tissue and the 
outer layers of the adventitia, but had failed to reach the inner 
tunics or lumen of the vessel. This experiment convinced him 
that the intact vessel-wall does not participate in the obliterating 
process. His numerous acupressure and torsion experiments 
showed that wherever obliteration of the vessels take place it is 
due to injury done to the intima, however slight that may be, 
followed by thrombosis, vascularization, and organization of the 
thrombus, and cicatrization by transformation of the white 
blood-corpuscles into cicatricial connective tissue, which finally 
approximates the inner vessel-walls, and holds them in perma- 55 
nent contact. He denies the possibility of direct union between 
the surfaces of the intima without the intervention of a throm- 
bus. The views so strongly advocated by Virchow, O. Weber, 
and' Kocher have been indorsed for the last forty years by a 
majority of the most prominent pathologists, and have found 
their way into most of our text-books. 
Paget writes: "The artery between the ligature and the 
nearest collateral branch contracts and in some instances oblite- 
rates the whole portion of the vessel, losing its anatomical 
features, and is gradually converted into a fibrous string. The 
colorless blood-corpuscles in the clot elongate into spindles, or 
form stellate corpuscles, such as are seen in young connective 
tissue, forming by anastomoses a network which traverses the 
clot in all directions."1 
Paget, however, recognizes the part performed by the vessel- 
walls, as he further states: "The clot, with the aid of the plastic 
inflammatory exudation, becomes firmly adherent to the inner 
walls of the vessel." Billroth, after his description of organized 
thrombi, accounts for the presence of the embryonal connective- 
tissue cells in the following manner: "After having abandoned 
the idea of proliferation of stable tissue-cells in inflammation, we 
can no longer talk of a proliferation of the intima in the old 
sense. But whence come, then, these newly-formed cells? I 
have no doubt that they originate from the white blood-cells, 
which have been partly inclosed in the thrombus, partly may 
have wandered into it, according to the observations of von 
Recklinghausen and Bubnoff."2 
XVII. Formation of Cicatrix from Red Blood-Corpuscles. 
The remaining pre-existing histological elements in the 
thrombus, the red blood-cells, have been considered as passive 
elements by the preceding authorities, destined to undergo 
granular degeneration and to disappear by absorption. A few 
1 Lectures on Surgical Pathology, 1870. 
2 General Surgical Pathology and Therapeutics, trans, by C. E. Hackley, A.M., 
M.D. N. Y. 1872, p. 108. 56 
pathologists, however, among them Rindfleisch, Adreef, and 
Koslowsky, assign to them an active part in the organization of 
the clot, for the reason that they have observed that instead of 
undergoing molecular disintegration they gradually lose their 
coloring material, and by a series of successive changes they are 
transformed into white blood-corpuscles and become endowed 
with all the intrinsic vital properties possessed by these elements. 
They maintain for the red blood-corpuscles the same active role 
in the organization of the clot and process of cicatrization as has 
been assigned to the white blood-corpuscles. 
XVIII. Formation of Cicatrix from Immigration Corpuscles. 
Soon after the discovery of the wandering corpuscle this 
element was supposed to be the principal agent in the process 
of tissue regeneration and in the formation of pathological pro- 
ducts. The obscure and much vexed question of obliteration 
of vessels after ligation found a ready interpretation by assuming 
that these wandering corpuscles, endowed with inherent properties 
to produce new tissue, would penetrate the walls of the vessel 
and enter its lumen, and there, by being converted into connec- 
tive tissue, would effect definitive closure. The functions pre- 
viously attributed to the pre-existing white blood-corpuscles in 
the thrombus was now assigned to immigration corpuscles by a 
number of observers, von Recklinghausen adopted this theory, 
and was soon followed by one of his pupils, Bubnoff, who wrote 
a lengthy and interesting article on this subject.1 In order to 
prove that cells enter the vessel from without he tied the jugu- 
lar vein in animals, and applied finely powdered cinnabar to the 
vessel at the seat of ligature before closing the wound. From 
the well-known capacity of the white blood-corpuscles to absorb 
finely divided substances, he expected that they would absorb 
some of these minute granules of the coloring material and con- 
vey them into the vessel, which would, on subsequent exami- 
nation, render their identification in the lumen an easy matter, 
1 Ueber die Organization des Thrombus, Centralbl. f. d. Med. Wiss. 1867, 
No. 48. 57 
and furnish positive proof of their passage through the vessel 
walls. He was not disappointed in his expectations, as in all of 
his experiments he found on microscopical examination cor- 
puscles charged with granules of cinnabar in the interior of the 
vessels. His results led him to adopt the following conclusions: 
The colorless blood-corpuscles in the thrombus lose their prop- 
erty to migrate after coagulation has taken place, consequently 
they take no active part in cell-proliferation. The organization 
of the thrombus is, to a great extent, accomplished by cells 
which enter the veins from without. Most of the cells are de- 
rived from the vasa vasorum and the adjacent para-vascular 
spaces. 
Kocher repeated these experiments on arteries, but failed to 
find the same results. 
Thiersch objects to the conclusions advanced by Bubnofif, 
claiming that the discovery of cells containing granules of cinna- 
bar in the interior of the vessels is no proof that the cells entered 
from without, as the coloring material might have entered the 
vessel with fluids passing through spaces in the vessel-walls 
without the assistance of any morphological elements. Raab 
admits that leucocytes do penetrate the coats of veins, but does 
not believe that they take any part in the obliteration of the 
vessel. Durante, Cornil and Ranvier, have demonstrated that 
leucocytes traverse the walls of a vessel only when this has been 
tied with a double ligature causing death of the included vessel, 
and that leucocytes travel only through this dead tissue. Klein1 
claims that endothelial cells are converted into leucocytes, and 
that these are instrumental in the process of cicatrization. 
Seuftleben2 has demonstrated beyond all doubt that leucocytes 
do enter the walls of veins which have been separated from all 
vascular connections. He removed sections of veins, disinfected 
them thoroughly, tied both ends firmly, and introduced them 
into the peritoneal cavity of living animals. He killed the 
animals at variable periods after the operation and found these 
1 The Anatomy of the Lymphatic System, London, 1873, I. 
2 Ueber den Verschluss der Blutgefasse nach Unterbindung, Virch. Arch., B. 77, 
S. 421. 58 
bloodless transplanted pieces of vein-tissue in most instances 
adherent and encysted. Even after a comparatively short time 
he found the interior of the vein occupied by masses of epithelial 
cells, spindle-shaped cells, round and even giant cells. The last 
mentioned cells were evidently intended to accomplish the work 
of absorption of the transplanted tissues. To all of these cells 
Seuftleben assigned an extra-vascular origin. 
N. Schultz1 studied the influence of the migration corpuscles 
in cicatrization in bloodvessels by applying a double ligature 
and excluding the blood from the intermediate portion of the 
vessel. He operated on arteries. In examining specimens a 
short time after operation he scraped the intima, and observed 
incipient degenerative change in the endothelia and no attempt 
at proliferation. In specimens two days old he found white 
blood-corpuscles in the lumen of the intermediary portion of the 
vessel which he believed entered from without, and which are 
eventually converted into connective tissue. In specimens 128- 
15 5 days old, the vessel between the two ligatures consisted of 
a string of loose connective tissue in which no trace of the 
original tissues of the arterial coat remained. Cicatrization pro- 
gressed more rapidly in the femoral than in the carotid arteries. 
In case only one ligature is applied he also observed no pro- 
liferation on part of the endothelial cells, but in this instance 
he believed that the process of organization and cicatrization of 
thrombus is due to the presence of the white corpuscles in the 
thrombus. 
Uhle and Wagner2 credit the wandering corpuscle at least 
with a part of the work required in the obliteration of a vessel. 
Their description of the cicatrix formation commences with the 
following allusion to this subject: " The organization of a 
thrombus is certainly not effected by an exudation on the inner 
surface of the walls of a vessel, nor by the white blood-corpuscles 
contained in it; perhaps at least in part it is due to the white 
blood cells circulating in the blood, and which gain entrance 
1 Ueber die Vernarbung von Arterien nach Unterbindungen u. Verwandungen, 
Deutsche Zeitschr. f. Chir. ix. 
2 Handbuch der allgemeinen Pathologic, Leipsig, 1876. 59 
into the vessel from the vasa vasorum, or by cells which origin- 
ate outside of the vessel walls, and by permeating them enter 
the lumen of the vessel." Billroth, after speculating on the 
origin of the white blood-corpuscles, says that they may spring 
from connective tissue or a protoplasm analogous to connective 
tissue, and he believes that they may traverse the living walls 
of vessels, as he has performed Bubnoff's experiment successfully 
on the carotid artery of a dog. 
One of the strongest arguments in favor of the tissue-pro- 
ducing function of the wandering blood-corpuscles is advanced 
by Ziegler.1 His experiments consisted in introducing under 
antiseptic precautions into the living tissues of animals, two glass 
plates with a capillary space between them. On examining 
the specimens at different intervals of time he found the space 
between the glass plates at first filled with white blood-corpus- 
cles which were subsequently transformed into connective tissue 
and bloodvessels. The results of these experiments have made 
Ziegler an ardent advocate of the doctrine that the wandering 
corpuscle is the principal tissue-producing element in all regener- 
ative and pathological formations. Every one must admit that 
these experiments are both ingenious and beautiful, but the 
deductions may lead to erroneous conclusions, as the experiments 
do not preclude the possibility of the entrance of embryonal 
connective-tissue elements from the wounded surfaces surround- 
ing the glass plates. In many instances the obliterating process 
is accomplished in such a remarkably short time that this theory 
would hardly apply, and until more positive evidence is furnished 
we must seek for a more satisfactory explanation. 
XIX. Formation of Cicatrix from Endothelia. 
The majority of the older authors who maintained that direct 
and primary adhesion of the inner walls of the vessel takes place 
after ligature, attributed this occurrence to a plastic exudation 
1 Experimentelle Untersuchungen uber die Herkunft der Tuberkel elemente, 
Wurzburg, 1875. 60 
upon the free surface of the intima. In entertaining this idea, 
they must have necessarily assumed that the tissues of which 
the intima is composed are capable of entering into tissue pro- 
liferation subsequent to the traumatism inflicted by the ligature. 
This doctrine was annihilated by Virchow, who taught that the 
intima does not respond to any amount of stimulation, and that, 
if the irritation is increased to a certain degree, necrosis of the 
intima takes place as a constant and unavoidable result. For 
a long time it was claimed that the intima takes no active part 
either in the organization of the thrombus, and the process of 
cicatrization. The advancements made in histology and the 
experimental investigations which have characterized the history 
of medicine for the last forty years have thrown new light upon 
the subject. The important part taken by stable tissue cells in 
all regenerative and pathological changes is again fully realized 
by the most competent observers, and the presence of inflam- 
matory changes in the intima after ligature is now fully estab- 
lished. 
His1 pointed out the difference between epithelia and endo- 
thelia, and showed that the latter originate exclusively from the 
mesoblast, belonging, therefore, to the series of connective- 
tissue formations possessed, like all analogous structures, of the 
common property of being capable of entering into tissue pro- 
liferation. As early as 1824, Rokitansky taught that primary 
union of the vessel-walls and definitive obliteration could take 
place independently of the formation of a thrombus. He 
believed that the surfaces of the intima adhere nearest to liga- 
ture, and the process of obliteration proceeds from this point to 
where collateral circulation is established. The vessel obliterates 
as it has no further physiological function to perform. He was 
never able to discover any vessels in the thrombus. 
Cohn2 was the first to assert that obliteration of a vessel after 
ligation is due to proliferation of the endothelial lining of the 
intima. Lancereux in France and Forster in Germany adopted 
his views. 
1 Die Haute und Hohlen des Korpers, Basel, 1866. 
2 Klinik der embolischen Gefasskrankheiten, Berlin, i860. 61 
Waldeyer, who is a firm believer in the endothelial origin of 
the intra-vascular cicatrix, describes the process of organization 
of the clot after ligature as follows: " The intima is rendered 
vascular from the media. From the intima loops of capillary 
vessels project into the thrombus accompanied by an envelope 
of delicate spindle-shaped cells from the endothelial lining, 
which constitute the basis of the future connective tissue."1 
Thiersch2 has studied experimentally the process of oblitera- 
tion in small vessels in wounds of the tongue of the Guinea pig. 
At the point of injury, both in arteries and veins, he has wit- 
nessed the rapid production of endothelial cells to which he 
attributed the most important function in the organization of 
the clot and obliteration of the vessel. 
Czernay3 claims that organization of the clot is complete five 
days after ligation. Although he refers this process to the 
presence of white corpuscles which accumulate in the thrombus 
and the vessel-walls, he satisfied himself that the endothelia at 
and near the seat of the ligature multiply with great rapidity. 
Baumgarten4 has made some very interesting experiments to 
establish a proliferation capacity of the endothelia. He asserts 
that obliteration of a vessel takes place without the intervention 
of a thrombus, as when the column of blood is excluded 
between two ligatures. He operated on rabbits by applying a 
double ligature both by excluding the blood in the intermediate 
portion of the vessel, or by leaving it between ligatures. In 
both instances he obtained prompt obliteration of the vessel. 
In case the blood was excluded from the vessel, he observed a 
cellulqr product in the lumen of the vessel a few days after 
operation; these cells he believed to be the product of endo- 
thelial tissue proliferation which was most marked in the imme- 
diate vicinity of the ligatures. The modified endothelia are 
1 Zur pathologischen Anatomie der Wundkrankheiten, Virchow's Arch. vol. xi. 
P- 379- 
2 Ueber den Verschluss der Gefasse bei Acupressur, Centralbl. f. d. med 
Wissensch., 1868, No. 50. 
3 Von Pitha u. Billroth's Handbuch der Chirurgie, vol. i. part ii. 
4 Ueber die sogenannte Organisation des Thrombus, Centralbl. f. d. med. Wiss., 
1876, No. 34. 62 
converted into fibroblasts (Neumann) and spindles of connective- 
tissue cells. When a thrombus was present, the granulation 
tissue gradually displaced the thrombus, and was finally con- 
verted into vascular connective tissue. The vascularization 
always took place by vessels from vasa vasorum. The ligatures 
were tied with sufficient force to divide the two internal coats. 
By applying an irritant to the outer surface of veins, he also 
noticed after twenty-four to forty-eight hours proliferation from 
the endothelial lining of the intima. The endothelia enlarged 
and assumed a cuboidal shape, showing conclusively that they 
participated in the inflammatory process which affected the 
entire thickness of the vein-walls. For one of the most valua- 
ble contributions to our knowledge of cicatrization in blood- 
vessels after ligature we are indebted to Fritz Raab.1 His 
experiments were made on dogs, and always under antiseptic 
precautions. The sheath of the vessel was opened at two places 
from 1-4 ctm. apart, and after tying the proximal ligature in 
the case of arteries, and the distal ligature in case of veins first, 
the blood was squeezed out of the vessel before tying the second 
ligature, securing thus a bloodless space between them. He 
cautioned against opening the sheath extensively for fear of 
producing necrosis in the intermediate section of the vessel. 
As ligature material, silk was used which was always cut short. 
If the ligature cuts through or the wound does not heal promptly, 
a funnel-shaped sinus remains which leads to the ligature, and 
in all of these cases the portion of the vessel-walls towards the 
wound was found destroyed. 
Experiment No. I.-Carotid artery; intermediate portion of ves- 
sel between ligatures two ctm. Animal killed after 12 days. At 
seat of ligature, artery, vein, and vagus blended in a spindle- 
shaped indurated mass of connective tissue. Vessel, between liga- 
tures, completely obliterated. Adventitia slightly infiltrated with 
cells. Media and intima normal. Endothelial lining changed into 
several layers of oblong spindle-shaped cells. Where surfaces of 
intima were brought into apposition the lumen was found obliterated. 
Remnants of blood-cells were also found which had remained in 
1 Ueber die Entwickelung der Narbe im Blutgelass nach der Unterbindgung. 63 
contact with inner walls of vessel. No vessels in the endothelial 
layers except at the seat of ligatures where intima and media had 
been circularly divided. Silk ligatures not infiltrated with cells. 
Under ligatures, fibres of adventitia remained intact. Proximal 
coagulum two ctm. in length, between folds of intima new endo- 
thelial formations. 
Experiment No. II.-External jugular vein ; ligatures four ctm. 
apart. Animal killed on 12th day. Around vein some induration. 
On distal side thickening of vein-walls; lumen smaller, containing 
a brittle red brown coagulum. Between ligatures, and two inches 
on proximal side, the vessel was transformed into a fibrous cord. 
Between ligatures all coats of vessels changed. Endothelia multi- 
plied and converted into spindle-shaped cells; between them em- 
bryonal connective-tissue cells and round cells. No vessels except 
close to ligatures where vessels from vasa vasorum had penetrated 
the interior of the vein. 
In commenting on these cases he gives his views concerning 
the formation of the intra-vascular cicatrix. Slight irritations 
will produce remarkable morphological changes in the endo- 
thelial cells. The walls of the veins do not require a great 
amount of traumatism to produce these results. During the 
first forty-eight hours after ligation, marked changes are ob- 
served which gradually extend from seat of ligatures to a certain 
distance, and it is immaterial whether the vessel contains blood 
or whether it has been rendered bloodless between ligatures. 
The first changes in the endothelia consist in an enlargement of 
the nuclei which imparts to the intima an increased wavy 
appearance. Later, the nuclei enlarge towards the periphery of 
the cells, displaying the protoplasm so that the protoplasmic 
spaces are diminished. The cells at this time assume a poly- 
hedric or rounded contour. The naked eye now detects a loss 
of the glossy surface of the intima. Similar changes can be 
observed in the endothelial lining of small arteries and veins in 
inflamed tissue. The sharp contour of the nuclei is lost as soon 
as the cells have attained a certain size. The protoplasm is 
interspersed with fine molecules which aggregate at three or 
four points, and the cell soon contains from three to four nuclei. 64 
Other smaller or pyriform or spindle-shaped cells are found in 
immediate contact with the large cell. These new cells originate 
from nuclei, and leave the cell-wall by the budding process. 
These small or daughter-cells are found in the lumen of the 
vessel on the surface of the endothelial layer. They become 
flattened, and eventually assume the shape of the old cells. 
They are variable in shape, according to the stage of develop- 
ment and locality in which they are found. In the folds of the 
intima they are flat, spindle-shaped, and elongated; on the 
surface, towards the lumen of the vessel, round or polyhedral. 
The proliferation takes place in the bloodless space as rapidly 
as when a thrombus is present. The obliterating process is 
completed earliest near the ligatures. In veins the round 
cells are most numerous, while in the arteries the flat spindle- 
shaped cells predominate. As the connective tissue is in closer 
proximity to the endothelial cells in veins than in the arteries, 
the proliferating process cannot be observed so satisfactorily as 
in the latter vessels. For the same reason the proliferation of 
endothelia begins later in arteries, and the process is accom- 
plished less rapidly. At first the proliferation is witnessed in 
the folds of the intima in the shape of spindle-shaped cells 
which fill the spaces between the elevations forming bridges 
from one fold to another. While in the normal intima the 
endothelial lining consists of two or more layers of cells, in the 
inflamed intima an amorphous mass is found which is interspersed 
with cells of high refractive power. These new cells accumu- 
late in great numbers, and finally perforate the endothelial lining 
into the lumen of the vessel. Heubner found the same condi- 
tions in examining specimens of endarteritis in vessels of the 
brain. In contradistinction to Heubner, Raab considers the 
cells on the surface of the endothelia as new productions. The 
nutritive supply for the endothelia is not derived from the blood 
circulating in the vessels, but is derived from the vasa vasorum 
of the adventitia. 
The cement substance liquefies and gradually disappears 
during active proliferation. If the inner surfaces of a vein or 
artery are kept in mutual contact primary union takes place at 65 
once by means of long spindle-shaped cells which are the pro- 
duct of the endothelial cells. The space between the surfaces 
of the intima occupied by these cells is finally completely oblit- 
erated and the inner coat is transformed into one tissue. If a 
thrombus is present the embryonal cells of the intima send pro- 
longations into the thrombus which unite with similar projections 
of other cells, thus forming a complete network of protoplasmic 
strings permeating the entire coagulum. Upon these strings 
new nuclei appear. These nuclei are the product of an aggre- 
gation of molecules, the connecting strings between the nuclei 
become narrower and eventually disappear, setting free the 
nuclei as new tissue elements. Some of the large spindle- 
shaped cells divide into two or more cells. The spindle-shaped 
cells arrange themselves into bundles with spaces between them 
which contain blood-corpuscles; these spaces may easily be 
mistaken for new bloodvessels. The endothelial product is not 
supplied with vessels until the tunics participate in the process, 
when vascularization takes place from the vasa vasorum. Ob- 
literation can take place by tissue derived exclusively from the 
intima, but all coats of the vessel assist in the process from the 
beginning. The connective tissue immediately beneath the 
swollen endothelial cells is rendered loose and succulent, the 
spaces between the individual bundles are widened and an 
occasional cell is seen in them. Towards the periphery of 
the vessel the spaces between the elastic tissue fibres are also 
widened and active infiltration of cells is also witnessed here. 
These cells, like the endothelia, send out projections in the form 
of long strings of protoplasm, forming networks with the con- 
nective-tissue interspaces. The connective tissue between elastic 
fibres proliferates. The connective and elastic tissue spaces are 
populated with cells of various shapes and sizes. We find here 
cells in all stages of division, large, round, polygonal, and pyri- 
form shaped, containing in their interior from two to four 
smaller cells. Around the vessels of the adventitia round lym- 
phoid cells appear which infiltrate all the tissues of the vessel. 
The microscopical appearances resemble in many respects the 
picture presented by the inflamed tissue in the cornea or carti- 66 
lage. Finally the new tissues perforate the endothelial layers 
and enter the lumen of the vessel, and mingle with the products 
of the endothelial cells, forming a common cicatricial tissue as the 
elements are being converted into connective tissue. Vessels of 
the adventitia enter through the coats of the vessel into its lumen, 
but the principal vascular supply of the intra-vascular tissues is 
derived from vessels which enter near the ligature through the 
spaces made by the circular division of the inner coats by the 
ligature. The ligature not only produces circular division of 
the inner coats but also longitudinal lacerations of the intima. 
The extent and degree of laceration of the walls of the vessel 
are in direct proportion to the amount of granulation tissue 
which is formed subsequently. Under the most favorable cir- 
cumstances direct union of the inner surface of the intima takes 
place exclusively by endothelial proliferation without a granu- 
lative thrombus. Where this result is not obtained the granu- 
lation tissue is formed first, and advances from the seat of liga- 
ture towards and into the lumen of the vessel where it unites 
with the endothelial product and produces the tissue which has 
heretofore been known as the organized thrombus. The granu- 
lation tissue is composed at first of cells, later of cells, fibres, 
and vessels, and finally the number of cells is diminished and 
the connective tissue is increased, when the vessel is reduced in 
size being ultimately converted into a string of connective tissue. 
Riedel,1 studied the process of cicatrization in bloodvessels 
experimentally in the same manner as the preceding author and 
arrived at similar conclusions. He used catgut in place of silk, 
and dogs and rabbits were made the objects of his experiments. 
The space between the ligature was made bloodless by isolating 
the vessel, raising it from its bed, and placing a spatula under- 
neath. In two of the specimens the interior of the intervening 
portion of the vessel was found obliterated. One specimen was 
obtained 9 days and the other 63 days after ligation. In the 
former specimen the endothelial proliferation appeared in the 
1 Die Entwickelung der Narbe im Blutgefass nach der Unterbindung, Deutche 
Zeitschrift fur Chirurgie, vol. vi. p. 450. 67 
shape of spindle-shaped connective-tissue cells which filled only 
two-thirds of the lumen of the vessel. In the second specimen 
the connective tissue in the interior of the vessel was distinctly 
fibrillated. The elastic layer of the intima had suffered in many 
places a loss of continuity to give passage to bloodvessels from 
the media into the thrombus. In the next experiment two 
ligatures were applied one ctm. apart, including a column of 
blood. The animal was killed on the ninth day. In place of 
the white blood-corpuscles in the red thrombus large cells con- 
taining from one to three nuclei were found; the cell contents 
were either granular or round globules of a yellowish color. 
The identity of these globular masses with the red blood-cor- 
puscles deprived of the greater part of their coloring matter was 
unmistakable. Some of these large cells appeared shrunken, 
with irregular surfaces, denoting incipient disorganization. 
While these cells were found uniformly present throughout the 
intervening portion of the vessel, the endothelia, half way between 
the ligatures, remained unchanged. Nearer the ligatures the 
endothelial layer was much thickened, filling completely the 
longitudinal folds of the intima. On the surface of the thick- 
ened endothelial lining were thin flat cells, and behind these 
new endothelial cells were seen the embryonal connective-tissue 
cells arranged irregularly with a variable amount of intercellular 
or cement substance. In other transverse sections, through por- 
tions of the vessel between the ligatures, could be seen springing 
from the parietal proliferation of the endothelial layer delicate 
processes penetrating the thrombus and reaching into the 
interior of the vessel and uniting with similar processes from 
the opposite side. These processes carried with them a layer 
of endothelia. At a right angle with these processes could be 
seen similar structures, thus dividing the interior of the vessel 
into spaces lined with endothelia. As the ligatures are ap- 
proached these spaces grow smaller, containing in their interior 
well preserved red corpuscles and the large cells previously de- 
scribed. Any active part on part of the blood-corpuscles in this 
process could be safely excluded, and cicatrization could be re- 
ferred exclusively to the action of the endothelial cells. The 68 
question presented itself whether the same process takes place 
in a thrombus not included between ligatures. To furnish a 
satisfactory answer, a thrombus, 27 days old, in the femoral 
artery of a dog was examined. The appearances presented 
were identical. The network of vessels in the thrombus com- 
municated directly with the vessels of the media. Injections 
made into the lumen of the vessel sometimes followed processes 
from the lining of the vessel and filled the spaces in the throm- 
bus. About the seat of the ligatures the external coats were 
actively engaged in aiding the processes of cicatrization. The 
connective tissue proliferates, the new cells being directed in 
such manner that they point towards the lumen of the vessel. 
They approach the intima accompanied by bloodvessels, pene- 
trate the membrana fenestrata, and unite directly with the endo- 
thelial formations. The spaces in the membrana elastica of the 
intima increase in size as the ligatures are approached so that 
in place of circular necrotic pieces of tissue large cicatrices are 
formed. Ligatures always produce necrosis of tissue underneath. 
A thrombus, 12 days old, showed the endothelial proliferation 
in the form of cells corresponding to the windings of the elastic 
intima. The membrane projected into the lumen of the artery. 
The conical end of the thrombus is also covered with endothe- 
lial cells. 
It is a well-known fact that connective tissue can be trans- 
formed into endothelial cells, as has been repeatedly observed 
in the formation of new synovial sacs. A thrombus not included 
between ligatures receives its first vascular supply from the 
lumen of the vessel. When blood is included between two 
ligatures, a scanty network of vessels reaches the lumen of the 
vessel from without. 
Uhle and Wagner1 testify positively to the importance of the 
functions of the endothelial cells and connective tissue in intra- 
vascular cicatrization in the following language : " In all proba- 
bility the most important structures in the process of organization 
are the endothelial cells and connective tissue of the intima. 
1 Handbuch der allgem. Pathologie. Leipsig, 1876. 69 
These proliferate within a few hours after ligation, and are first 
transformed into spindle-shaped cells, and later into connective 
tissue and vessels. As early as six or eight days after the 
formation of the thrombus, especially towards its periphery, it is 
traversed by a network of young capillary vessels which increase 
rapidly for the next few days. During this time the fibrin and 
blood-corpuscles disintegrate in the same manner as the so- 
called dissolution of the thrombus. The new vessels in the 
thrombus and intima enter into communication with the original 
and new vessels of the media and adventitia, and thus a genuine 
circulation is established throughout the entire thrombus ; later 
an anastomosis is formed between the vessels in the thrombus 
and the lumen of the vessels. Reparative changes are initiated 
at first in the immediate vicinity of the ligature. After four to 
six weeks the circulation in the thrombus is completed, when 
the vessels again gradually disappear, the cement substance 
grows firmer, the red blood-corpuscles and fibrin, which still 
may remain are absorbed. At last only a minute connective- 
tissue string remains which can only be recognized by the aid 
of a microscope." 
Cornil and Ranvier1 have carefully investigated the part taken 
by the endothelia in cicatrization within bloodvessels after liga- 
ture. The following is a summary of their observations: 
Within 24 hours after ligation a clot forms in the central end 
which reaches to the nearest collateral branch. At this time 
the endothelia are swollen and granular, containing a round 
nucleus and frequently several nuclei. On the following day 
the thickening of the intima is well marked, especially near the 
ligature. The thickening of the internal coat is due to a pro- 
liferation of cells which appear spindle-shaped, but in truth they 
are flat. They resemble endothelia or cells of connective tissue 
swollen by inflammation. On the eighth day the internal coat 
puts forth low elevations, nipple-like in shape, which are particu- 
larly well marked at the point of ligation. By the 12th to the 
15th day these elevations on the cardiac side of the ligature 
1 A Manual of Histology, by Shakespeare and Simes. Philadelphia, 1880. 70 
penetrate into the blood clot, accompanied by capillary blood- 
vessels which run parallel to the axis of the elevations. In 
longitudinal sections it is seen that, at the place of implantation 
of these projections, the middle coat of the artery has disap- 
peared so that they appear to spring from the external coat. 
Their vessels are derived from the vasa vasorum. The clot 
disappears before the new tissue, the spaces between them being 
occupied by discolored red blood-corpuscles, granules, and a few 
white corpuscles, an appearance which simulates blood chan- 
nels as described by O. Weber. 
I will mention a few recent American authors who assign to 
the endothelia an important, if not essential, function in the 
formation of the intra-vascular cicatrix. 
Shakespeare* has made a number of experiments to deter- 
mine what histological elements are active in the obliteration of 
vessels after ligation, and his views are summarized in the fol- 
lowing : An acute endarteritis follows ligation, during which the 
endothelia and other cellular elements of the intima multiply 
with great rapidity. The inflammatory changes are most 
marked near the ligature. New cells are usually flattened and 
more or less endothelial in appearance. Among these large 
endothelioid cells are a considerable number of lymphoid cells 
and a few red blood-corpuscles. The cement substance holding 
these elements together, is sometimes structureless, sometimes 
granular, and occasionally slightly fibrillar. In a few days the 
walls of the plastic clot begin to bud and put forth granulations 
which encroach upon the space between the inner surface of the 
vessel and the blood clot, and upon the blood clot itself. The 
granulations by pressure and absorption remove the clot. The 
granulations have much the same structure as granulation tissue 
in any other part of the body. They are covered by a layer of 
endothelial cells. The base of the granulations rests upon the 
elastic lamina of the intima which, up to the 20th or 25th day, 
remains unchanged, forming a sharp boundary between the 
middle coat of the artery and the proliferation of the intima. 
1 Cornil and Ranvier's Manual of Histology, p. 322. 71 
There is usually no indication of its perforation by capillary 
loop from the vasa vasorum. As the projections of granular 
tissue approach each other, sinuses are formed in which the 
blood circulates and supplies capillary vessels which at this time 
are formed at the bottom of the plastic clot. At the same time 
capillary varices form in the embryonal tissue of the outer coats 
of the vessel in the neighborhood and at the location of the liga- 
ture. They receive their blood from the vasa vasorum. In a 
few days the two capillary systems form a communication with 
one another by means of connecting loops which perforate the 
space between the injured elastic membrane of the intima at the 
point of ligature. The granulation tissue undergoes cicatrization 
and contraction which obliterate the vessel. The author 
describes at some length the laminated structure of the throm- 
bus, and it is evident that the vascular networks in the thrombus 
were simply spaces between the lamina which were occupied 
by the pre-existing blood corpuscles in the thrombus, and that 
vascularization took place exclusively from the vasa vasorum. 
Agnew1 believes that the production of the new tissue may 
be accomplished by white blood-corpuscles, endothelia, and 
migrating corpuscles. 
Lidell2 holds that the thrombus undergoes organization, but 
attributes the definitive closure to adhesive inflammation of the 
inner and middle coats, the plastic exudation from the adventitia 
adding additional strength to the walls of the vessel. In speak- 
ing of the same process in veins he says: "Again, veins may, 
and often do, undergo repair after ligature without any inflam- 
mation whatever, whether adhesive or otherwise, as Mr. Travers 
was the first to show." 
Wyeth3 takes a more advanced ground and regards the endo- 
thelia as the essential element in effecting definitive obliteration. 
He writes: "The permanent occlusion is due to new-formed 
tissue springing from the normal cells of the intima." 
1 The Principles and Practice of Surgery, vol. i. p. 155. 
2 Injuries of Bloodvessels, Intern. Encyclop. of Surgery, 1883, vol. iii. 
3 Surg. Diseases of the Vascular System, Intern. Encyclop. of Surgery, vol. iii. 
P. 351- 72 
Heitzmann says: "Occlusion of ligated vessels is due mainly 
to endothelial proliferation, and vascularization of the thrombus 
starts in the inflamed intima."1 
The fact that endothelia are endowed with sufficient vitality 
to proliferate new tissue is, however, not based alone on the 
observations of practical surgeons and experimental research, it 
is also supported by pathological processes which affect the 
inner tunics of the vessel. Virchow, in his experiments on 
embolism, introduced triangular pieces of rubber into the right 
heart through the external jugular vein. After four weeks he 
found the piece of rubber impacted in a branch of the pulmo- 
nary artery encysted in a vascular capsule composed of spindle- 
cells and flat-cells, evidently products of the endothelial lining. 
The inflammatory changes which occur in the endothelia of 
serous membranes have been studied by Rindfleisch, Klein, and 
Cornil and Ranvier. Kundrat selected for his investigations the 
peritoneum, Chapman the pericardium, and Albert the synovial 
membranes. Ponfick has called special attention to the rapid 
changes which take place in the endothelia during the acute 
stage of infectious diseases, and Heubner has assigned to them 
a special susceptibility for the syphilitic virus. Although O. 
Weber2 takes it for granted that thrombosis and organization of 
the clot are the two essential conditions which precede and ac- 
company the definitive obliteration of a vessel, he states distinctly 
that he has seen the endothelia repeatedly in a condition of so- 
called cloudy swelling, which would indicate that he has wit- 
nessed the first stage of progressive tissue metamorphosis in 
these structures-the first stage of inflammation. 
Friedlander3 has described a heretofore unknown affection of 
the arterial coats which he has called "arteritis obliterans." The 
affection is located in the intima of arteries of medium and 
smallest calibre and results in stenosis and sometimes complete 
obliteration of the vessel. The process is inaugurated by the 
* Microscopical Morphology of the Animal Body in Health and Disease, N. Y. 
1883. 
2 V. Pitha u. Billroth's Handb. d. allg. u. spec. Chir. vol. ii. div. ii. part i. 
s Ueber Arteritis obliterans. Centralblatt f. d. med. Wiss. No. 4, 1876. 73 
appearance of numerous round-cells between the innermost 
lamellae of the elastic layer and the endothelial lining. The 
cells increase in size, intercellular substance is formed, and the 
new product presents all the characteristic appearances of granu- 
lation tissue with an abundant supply of new vessels, some of 
which are of considerable size. The proliferation may be 
limited to small points, or it may involve the entire circumfer- 
ence of the vessel. The new-formed tissue is generally con- 
verted into dense connective tissue, seldom undergoing fatty or 
calcareous degeneration. A physiological process very similar 
to the one described takes place during the occlusion of the 
ductus arteriosus Botah in the vessels of the umbilical cord after 
birth, and in the arteries and veins of the uterus after parturi- 
tion. Analogous changes are observed in the small vessels in 
tissues which are the seat of chronic inflammation. Heubner 
has described it as it occurs in the vessels of the brain, but he 
was wrong in asserting that it was caused by the specific effect 
of the syphilitic virus. Regarding the source of the cellular 
elements, he mentions three probabilities: I. Either they are 
the product of the endothelia of the intima; 2. They originate 
from white blood-corpuscles in the lumen of the vessel which 
must pass through the endothelial lining of the vessel; 3. Or 
leucocytes from the vasa vasorum. 
Friedlander is inclined to the belief that they are derived from 
all of the three sources. 
Winiwarter1 reports a case of spontaneous gangrene of the 
foot in a man 57 years of age, who presented no symptoms of 
atheromatous degeneration of the vessels. On submitting the 
vessels of the amputated member to a thorough microscopical 
examination, he found a proliferation of endothelial cells of the 
intima in the arteries and veins, which had produced narrowing, 
and, in some places, complete obliteration of their lumen. He 
found the proliferation most active in small vessels which are 
composed exclusively of endothelia. The endothelia increase 
1 Ueber eine eigenthuemliche Form von Endarteritis und Endophlebitis, Archiv 
f. klinische Chirurgie, vol. xxiii. p. 206. 74 
in size and assume a cuboidal shape, and as the proliferation 
advances the endothelial lining is thickened by additional closely 
packed layers of cells. In examining transverse sections of the 
smallest arteries, he observed the following appearances: The 
endothelial cells are arranged in concentric layers; towards the 
lumen of the vessel they are spindle-shaped and partly converted 
into connective tissue. In places where the vessel is not entirely 
obliterated, its lumen often appears irregular in outline, owing 
to the greater activity of tissue production in some portions of 
the inner walls of the vessel than in others. The media is also 
thickened partly by the increase of muscular fibres, and partly 
by cell infiltration from the intima. The cellular thrombus in 
the interior of the vessel is organized, and the cellular elements 
are gradually converted into connective tissue which completely 
and permanently obliterates the vessel, transforming it into a 
round string of connective tissue. In the interior of such strings, 
deposits of a homogeneous substance may be seen which indi- 
cate that retrograde metamorphosis of the cellular elements has 
occurred in place of organization into connective tissue. The 
same conditions were also found in veins. 
Baumgarten1 has found the vasa vasorum included in the 
ligature in ligating large vessels, a favorable locality to study 
this process. The inflammatory process begins in the adventi- 
tial structures, and extends by continuity to the endothelial 
lining, where proliferation takes place promptly and with con- 
siderable activity. Giant-cells may originate from endothelia, 
and, in case of very minute vessels, a single cell may block the 
calibre of the vessel completely. The endothelial cells, in the 
course of time, are changed into spindle cells, and finally into 
connective tissue. The round cells found in the media and 
adventitia undergo the same transformation. 
Cornil and Ranvier2 have seen several times cases of acute 
circumscribed endarteritis in the form of patches as an isolated 
lesion. Multiplication of the endothelia on the surface of the 
1 Ueber chronische Arteritis u. Endarteritis, Archiv f. path. Anatomic u. Phys., 
vol. Ixxiii. p. 90. 
2 A Manual of Histology, by Shakespeare and Simes, Phil. 1880, p. 307. 75 
internal coat is peculiar to acute endarteritis, while in the endar- 
teritis preceding atheromatous degeneration, the proliferation 
takes place in the deepest layer of the intima. Multiplication 
of cells takes place by division of nuclei. A careful study of 
the new elements demonstrates that they spring from the intima. 
Periarteritis always coexists. The external coat produces granu- 
lation tissue. In the middle coat proliferating elongated cells of 
smooth muscle are seen, while the elastic fibres are broken down 
and absorbed. 
As a last witness we will hear Heitzmann1 concerning the 
endothelia when subjected to irritation and in a condition of 
inflammation, without alluding to the peculiar views on proto- 
plasm entertained by this author. Endothelia being formations 
of living matter, are susceptible of undergoing rapid changes 
under the influence of irritation. The process is always secon- 
dary to affections of the subjacent vascular connective tissue. 
The inflammatory changes in this tissue as in every other con- 
sist in an increase of tissue. The endothelial cells in the initial 
stage become coarsely granular, or assume the " condition of 
cloudy swelling." The coarse granules increase in size, and 
constitute the inflammatory elements in all stages of develop- 
ment, reaching the highest development in the nucleated cells. 
The endogeneous new formation of elements within the epithelia 
was first maintained by Remak in physiological, and afterward 
by Buhl, Rindfleisch, and others in pathological conditions, and 
its existence thoroughly proved by L. Oser. In opposition to 
the supposition that the corpuscles visible in the endothelia had 
immigrated from without, Oser demonstrated the origin of in- 
flammatory corpuscles within the epithelia. Heitzmann corro- 
borates this view. A sufficient number of competent and 
reliable authorities have been cited, and enough has been said 
to prove that the vascular endothelia, when subjected to a suffi- 
cient degree of irritation, are susceptible of assuming inflamma- 
tory changes, and capable of proliferating new tissue elements 
which, if not the only reparative material, at least render essen- 
1 Loc. cit. 76 
tial assistance in the process of cicatrization after ligature. It 
is important, however, to remember that the process of endo- 
thelial proliferation is secondary to the inflammatory changes 
which take place in the vascular connective tissue. The periar- 
teritis and mesoarteritis which immediately follow ligation are 
attended by the formation of new bloodvessels which penetrate 
the intima, bringing the endothelial lining in direct contact with 
the circulation, which places the endothelia under the same 
conditions of nutrition and subject to the same pathological 
processes as any other vascular organs. 
XX. Formation of Cicatrix from Connective Tissue. 
The formation of the intra-vascular cicatrix from connective 
tissue has been frequently mentioned as the cause of the defini- 
tive closure of vessels since the introduction of the circular liga- 
ture by Jones. It was urged that the division of the two inner 
coats by the ligature and the curling inward of the lacerated 
tissues towards the lumen of the vessel would not only allow of 
the adventitia being brought in contact, but would also create 
a wound surface which would heal in the same manner as wounds 
in any other locality. The important function performed by the 
connective tissue in repairing solutions of continuity in any 
part or organ is well established and recognized by all authori- 
ties. The connective tissue is more widely diffused throughout 
the entire body and its susceptibility to undergo embryonal 
changes in a remarkably short time is as well known as its ca- 
pacity to produce various types of tissue. It is the tissue which 
is invariably present in all cicatricial formations. This tissue is 
present in all coats of the arteries and veins; it accompanies 
bloodvessels wherever they go, hence it is only reasonable to 
assume that it plays an important part in the reparative process 
in vessels after ligation. 
Kblliker and Eberth claimed that the connective tissue between 
the endothelial lining and the elastic layer of the intima pro- 
liferates and renders material assistance in the permanent closure 
of vessels. 77 
Durante believed that when only one ligature is applied, 
obliteration of the vessel takes place by proliferation of the 
intima; when the double ligature is used the media and adven- 
titia assume this office. 
Reinhardt, after declaring that the thrombus remains passive 
after ligature, asserts that obliteration of the vessel takes place 
by an exudation or blastema from the adventitia. 
Auerbach,1 under Koster's directions, studied the obliteration 
of vessels experimentally on dogs and rabbits after single and 
double ligation. In using the double ligature he compared 
the results obtained by excluding the column of blood in the 
intervening vessel with those cases where blood was included 
between the ligatures. He ascertained that those vessels fur- 
nish the most favorable conditions for obliteration where the 
intervening portion was moderately filled with blood. The first 
changes observed in the coats of the vessel after ligation was 
an inflammatory infiltration in the adventitia proceeding in a 
central direction toward the lumen of the vessel. The acute stage 
is followed by a chronic granulation process which is established 
almost exclusively in the adventitia and intima. The inflamma- 
tory infiltration appears earliest at the seat of the ligature and 
reaches here the highest degree of development. The intima is 
supplied with vessels from the adventitia. The definitive oblit- 
eration of the vessel is due entirely to connective-tissue prolifera- 
tion from the intima. The endothelia, although they manifest 
an attempt at progressive' metamorphosis, do not produce new 
tissue. In case the adventitia is injured or removed prior to 
operation no changes occur in the two inner coats. 
Roser2 asserts that obliteration of an artery often takes place 
without a thrombus, and that the essential structure in this pro- 
cess is the adventitia. After the two internal coats have been 
severed by the ligature the external coat is brought in contact, 
and union takes place in the same manner as in other wounds. 
1 Ueber die Obliteration der Arterien nach Ligaturoo. Dissertation, Bonn, 1877. 
Virchow u. Hirsch's Jahresb. 1878, vol. i. p. 233. 
2 Zur Theorie der Blutstillung u. d. Nachblutungen. Arch. f. klin. Chir., vol. xii. 
p. 223. 78 
As a frequent cause of secondary hemorrhage he mentions that 
small traumatic aneurisms sometimes form at the seat of liga- 
ture in the sac of the adventitia which rupture, and that in case 
of ligation of the artery in its continuity the tension exerted by 
the vessel increases the danger of rupture. In healthy animals 
occlusion of an artery takes place in a satisfactory manner even 
if it is tied in the immediate vicinity of a large branch. The 
same can be said of arteries which are ligated after amputations. 
Only in exceptional cases does obliteration take place through 
the medium of a thrombus. 
For the most thorough investigations respecting the definitive 
closure of vessels after ligation from connective-tissue prolifera- 
tion, we are indebted to Tschausofif.1 His experiments were 
made on dogs. The specimens for microscopic examination 
were hardened in Mueller's fluid for two to three weeks and 
subsequently immersed for two to three days in absolute alcohol, 
and finally a few days in turpentine, and for the purpose of 
making sections, they were incorporated in a cylinder composed 
of wax and stearin. He has carefully traced the tissue changes 
in specimens from I to 120 days old. In specimens three days 
old he noticed an increase in the size and number of the vessels 
in the external coat. At this time the connective tissue of the 
intima has undergone considerable development, the fibres being 
directed transversely to the lumen of the vessel and in immediate 
contact with the endothelial lining. In a thrombus of the bra- 
chial artery obtained eight days after ligation he found in trans- 
verse sections the vessels of the media and adventitia, and, to a 
lesser extent, of the intima stained blue from colored injections. 
The new connective-tissue formation of the media and intima at 
some points had gained entrance into the lumen of the vessel, 
reaching as far as the centre of the thrombus at certain places. 
In a specimen of the brachial artery nine days old the lumen of 
the vessel near the ligature was found completely filled with 
new connective tissue. In a specimen of the femoral artery of 
18 days all the tissues of the vessel showed a beautiful network 
1 Ueber den Thrombus nach der Ligatur. Arch. f. klin. Chirurg. 79 
of capillary vessels which were derived from the external coat. 
The original structures of the intima and media were at many 
points observed by the new formative tissue. The endothelial 
layer at some places was preserved, at some points indistinct, 
and at others completely obscured. The lumen was filled with 
a compact mass of organized tissue. In a thrombus of the 
brachial artery 20 days old the proliferation of connective tissue 
was seen to project beyond the endothelial lining of the intima. 
In a thrombus of the brachial artery 25 days old the endothelial 
lining was seen to be almost completely covered by new tissue 
in some places, while at others it was either indistinctly visible 
or somewhat thickened. The new connective-tissue fibres in the 
intima and media were disposed transversely, obliquely, and 
longitudinally. The lumen of the vessel was completely closed 
by new connective tissue, the most recent formation correspond- 
ing to the centre of the vessel, while vascularization increased 
in a peripheral direction. In a specimen of the carotid artery 
32 days old all tissues of the vessel-walls were stained by the in- 
jection fluid. The endothelial layer was covered partly or com- 
pletely with organized exudation material; near the ligature the 
endothelial cells had completely disappeared, and the fibres of 
the intima and media could no longer be seen. Lumen of 
vessel completely obliterated. Remains of thrombus consist of 
pigment granules. In a specimen of the femoral artery 40 days 
old only the external coat was discernible. The endothelial 
layer was expanded, infiltrating the intima. In a specimen of 
the femoral artery 50 days old the endothelial layer was ob- 
scured by new connective-tissue fibres; lumen near ligature 
obliterated. 
In a specimen of the carotid artery 60 days old the endo- 
thelial layer was found mostly covered with embryonal con- 
nective tissue, and at some points somewhat thickened. In a 
preparation of the femoral artery, obtained 120 days after oper- 
ation, the lumen occupied by a thrombus was not obliterated, 
but near the ligature the vessel was completely closed. The ves- 
sels in the walls of the artery were reduced in size and number. 
Endothelial layer in some places displaced by new tissue, at 80 
other points it can be distinctly seen. The young connective 
tissue in the lumen of the vessel is defined by the plicated endo- 
thelial layer, and adheres all around to the inner walls of the 
vessel. No vessels can be seen in the intra-vascular cicatrix. 
In commenting on these specimens, Raab alludes to the con- 
stancy with which inflammatory exudation takes place at the 
seat of the operation and ligature. The thrombus varies in size, 
and frequently does not reach as far as the nearest collateral 
branch. As a rule, the central thrombus is larger than the 
peripheral. Three to four weeks after ligature adhesion of the 
inner walls of the vessel takes place near the ligature by con- 
nective-tissue proliferation. The blood-corpuscles in the throm- 
bus become granular, disintegrate, and are absorbed. Dis- 
solution of the thrombus commences where organization of new 
tissue begins, that is, near the ligature and in the peripheral 
portion of the clot. That the pre- existing tissues in the coats 
of the artery are active in the process of obliteration is made 
evident from the fact that the walls of the vessel are invariably 
very much thickened. Tissue proliferation in the coats of the 
vessel could be observed in cases where no progressive changes 
could be recognized in the thrombus. No attempt at organ- 
ization ever took place prior to the fourth day. Vascularization 
of the inner tunics is attended by an active connective-tissue 
proliferation; the new tissue advances in a central direction and 
finally gains entrance into the lumen of the vessel. The best 
possible proof of the importance of the vessel walls in the pro- 
cess of obliteration is furnished by the fact that tissue prolifer- 
ation takes place within them, independently of the formation 
of a thrombus. The connective tissue, wherever found in the 
tunics of the vessel, takes part in the process, the endothelia, 
and muscle fibres of the media take no active part. The endo- 
thelial layer is perforated by the new connective tissue, or is 
pushed before it towards the centre of the lumen of the vessel. 
The final disposition of the endothelia and muscular fibres 
probably consists in atrophy and absorption. 
With the evidence before us we are certainly not warranted 
in assuming with Tschausoff that the endothelia are not sus- 81 
ceptible of tissue proliferation under such conditions as are 
created by the ligature. Endothelia and connective tissue have 
one common embryonal origin, and their relations are such that 
in the vessel-walls changes in one are very apt to extend to the 
other. Connective tissue can be transformed into endothelia, 
and there is no well-founded reason why the reverse should not 
occur. Even Tschausoff, who explains the whole process of 
cicatrization from a standpoint that the connective tissue is the 
only active element, volunteers the assertion that on several 
occasions he has seen the endothelial lining thickened, which 
certainly would imply tissue increase from pre-existing cell 
elements. 
After having excluded fibrin and the morphological elements 
of the blood within and without the walls of the vessels, as active 
agents in accomplishing definitive obliteration of the vessel after 
ligature, we are prepared to impute to the endothelial cells, and 
the connective tissue in the vessel-walls, the role of active agents 
in the formation of the intra-vascular cicatrix. Both of these 
histological elements are transformed into embryonal tissue 
which in turn is changed into mature connective tissue. The 
tissue proliferation is initiated at the point of greatest irritation, 
the seat of traumatism, and in the vascular adventitia; from 
these points it extends towards and into the lumen of the vessel. 
This process of tissue proliferation is attended by the formation 
of new vessels from the vasa vasorum, which permeate all tunics 
of the vessel and supply the intra-vascular thrombus of embry- 
onal tissue, which is finally converted into perfect connective tis- 
sue, and results in the definitive closure of the vessel. After the 
function of the vessel has been permanently abolished all remain- 
ing histological elements from non-use and cicatricial compression 
undergo atrophy and eventually disappear completely by 
absorption, leaving only a string of connective tissue to indicate 
the extent of the obliterated vessel. The vessels in the cicatrix, 
after having accomplished the purpose for which they were 
intended, gradually disappear, an occurrence which is followed 
by contraction and atrophy of the cicatrix itself. 82 
XXI. Primary Union in Bloodvessels after Ligature. 
By the healing of a wound by primary union we understand 
rapid repair without suppuration. Used in this sense the term 
could be appropriately applied almost to every case of ligation 
of vessels if the operation were done under antiseptic precautions. 
As applied to vessels after ligature this term however conveys 
another and still more significant meaning: it implies union 
between the inner surfaces of the lumen of an artery or vein in- 
dependently of the formation of a thrombus. The importance 
of guarding against suppuration, and of securing primary union 
of the wound, has been repeatedly alluded to as conditions which 
favorably influence the process of cicatrization in vessels. All 
conditions which impair normal healthy tissue proliferation at 
the seat of ligature affect unfavorably the reparative process 
after ligature. Atheroma of the tunics of the vessel, excessive 
inflammation and suppuration cannot fail to exert a deleterious 
influence upon the reparative process in the walls of the vessel 
after ligature. From what we have gleaned from the literature 
on thrombosis, tissue proliferation, and regeneration, we are 
justified in asserting that obliteration of a vessel after ligature 
takes place promptly without a thrombus, and further that the 
only function of the thrombus consists in furnishing a favorable 
soil for the development and maturation of the tissue which 
grows into the lumen of the vessel from the stable cells of its 
tunics, and which is destined to furnish the cicatricial tissue for 
permanent obliteration. Experiment and clinical observation 
furnish abundant evidence that closure of vessels frequently 
does take place without thrombus formation. The many cases 
of successful lateral ligation of large veins with preservation of 
the lumen of the vessel also speak in favor of primary union. H. 
Braun1 collected fifteen cases of lateral ligature of veins, of 
which number ten proved successful. Eliminating the thrombus 
as an active agent in the obliterating process, we can say that 
union between the tissues which are brought in contact by the 
1 Verhandlungen der Deutschen Gesellsch. fur Chirurgie, 1882. 83 
ligature takes place by tissue proliferation from the walls of the 
vessel itself. In its true sense direct or primary union never 
takes place, as in all instances closure is effected by granulation 
and cicatrization. In case the inner tunics are severed by the 
ligature, the lacerated surfaces are brought in contact with the 
adventitia, and repair takes place as in any other tissues which 
are largely composed of connective tissue, the process extending 
from both sides of the ligature where endothelia assist in the pro- 
cess of cicatrization. If, on the other hand, the continuity of the 
vessel is not destroyed by the ligature, and the intima is brought 
in contact, the connective-tissue proliferation perforates the en- 
dothelial lining, and the elements of the latter join in the repara- 
tive process by being converted into embryonal and subsequently 
into connective tissue. The first inflammatory changes in en- 
dothelia are observed near the seat of the ligature about the 
third day, and the use of the temporary ligature has demon- 
strated that in arteries about the size of the radial, even when 
the internal coats are ruptured, three to four days are necessary 
for sufficiently firm adhesions to take place to resist the intra- 
arterial pressure. 
While vascular tissues may unite firmly after twenty-four to 
forty-eight hours, as in wounds about the face or scalp, it re- 
quires from four to twelve days for the tissues of the vessel-walls to 
unite with the same degree of firmness. In the inner tunics of 
the vessels vascularization from the vasa vasorum must take 
place before tissue proliferation can advance to the requisite 
extent. 
In conclusion, we can say that wounds in bloodvessels inva- 
riably heal by granulation and cicatrization, and that when a 
ligature is applied the definitive intra-vascular cicatrix is formed 
in a similar manner. 
XXII. Experiments. 
After many trials the sheep was selected as the subject of 
most of the experiments, as it was found that this animal pre- 
sented the most favorable conditions for these operations. All 84 
operations were done under antiseptic precautions as far as cir- 
cumstances would permit. The surface was shaved, thoroughly 
cleansed, and disinfected with a five per cent, solution of car- 
bolic acid. Irrigation with a three per cent, solution was used 
occasionally during the operation, and always before closing the 
wound. The wounds were invariably completely closed with a 
continuous catgut suture, and hermetically sealed with salicylated 
cotton and iodoform coilodium. The vessel sheath was always 
opened to the extent of one inch or more, and the artery or 
vein completely isolated to the same distance, when two liga- 
tures were placed underneath the vessel. The proximal was 
tied first in tying arteries, and the distal in the case of veins, the 
vessel was made bloodless by placing the second ligature in close 
contact with the first and by making traction upon both ends, 
and sliding the loop to the required distance, when the return of 
blood was prevented by an assistant compressing the vessel be- 
tween the thumb and index finger until the ligature was tied. If 
any doubt remained as to the bloodless nature of the intervening 
space, these manipulations were repeated before tying the second 
ligature. In tying the ligatures it was aimed not to injure the 
internal coats but simply to approximate the inner surfaces of 
the intima so as to effect provisional closure of the vessel. The 
ligatures were usually applied about one-half to one inch apart. 
With the exception of the temporary all ligatures were cut short. 
In removing the temporary ligatures the coilodium dressing 
and suture were removed, and the vessel drawn towards the sur- 
face of the wound by making gentle traction on the ligature 
ends when the loop of the ligature was carefully cut with small 
curved scissors. After the necessary examination the wound 
was irrigated, closed, and dressed in the same manner as before. 
As an anaesthetic, ether, chloroform, or bromide of ethyl were 
used. The anaesthesia produced by the last was always of very 
short duration, while ether appeared to offer the greatest immu- 
nity against accidents. The illustrations are of natural size, and 
represent the whole specimen as removed from the animal and 
a cross section through the middle of the intervening portion. 
The two perpendicular lines at the extremities of the specimen 85 
show the location of the ligature, while the middle line denotes 
the place of the cross-section. I desire, in this place, to express 
my gratitude to my friend Dr. H. M. Brown, of Milwaukee, for 
the valuable aid rendered in preparing the illustrations for this 
article. 
Double Ligation of Arteries. 
Experiment No. i.-Right common carotid ligated with medium 
sized catgut. Animal died from the effects of the anaesthetic six 
hours after operation. Proximal thrombus two inches in length ; 
non-adherent. Minute distal thrombus in the folds of the intima. 
Inner coats of the vessel not injured by the ligatures. No appreci- 
able changes in walls of vessel. 
Experiment No. 2.-Left common femoral artery ligated with 
coarse catgut, the distal ligature immediately above the profunda. 
Animal killed 24 hours after operation. Proximal thrombus, none. 
Minute distal thrombus. Loop of ligature covered by swollen 
adventitia. Lumen of profunda not closed by thrombus. 
Experiment No. 3.-Right common iliac ligated with braided 
silk. Distal ligature immediately above bifurcation. Animal killed 
3 days after operation. Proximal thrombus, none. Minute mural 
thrombus in external iliac artery. No thrombus in internal iliac. 
On removing proximal ligature vessel was found closed beneath it, 
while the intermediate portion of vessel remained pervious. Loop 
of ligature covered by granulation tissue. 
Experiment No. 4.-Right femoral artery tied with coarse cat- 
gut. Animal killed 7 days after operation. Proximal thrombus 
extending to next collateral branch, three-fourths of an inch above 
the ligature; non-adherent, and filling only partly the lumen of 
vessel. Distal thrombus minute. Intervening portion of vessel 
filled with an adherent mass of granulation tissue. Ligatures 
softened and covered by granulation tissue. On removing central 
ligature lumen of vessel was found to be completely and firmly 
obliterated by direct adhesion between the surfaces of the intima 
(Fig. 1). 86 
Fig. I. 
Experiment No. 5.-Right femoral artery ligated with medium 
sized catgut, proximal ligature, immediately below the profunda. 
Animal killed 8 days after operation. Proximal thrombus about 
one inch in length, small, non-adherent, and not extending into the 
profunda, this vessel remaining pervious. Filiform peripheral 
thrombus. Intervening portion patent and adherent to surrounding 
tissues. Ligatures almost completely encysted ; vessel under proxi- 
mal ligature obliterated. 
Experiment No. 6.-Right femoral artery ligated with coarse 
braided silk. Animal killed 10 days after operation. Small globu- 
lar proximal thrombus. No peripheral thrombus. Intervening 
portion and ligatures inclosed by a fibrous capsule. Underneath 
distal ligature vessel walls adherent. Intervening portion on the 
side corresponding to the external surface is covered by a thick 
layer of granulation tissue. 
Experiment No. 7.-Left common carotid ligated with silkworm- 
gut ligature. Animal killed 11 days after operation. Proximal 
thrombus three inches in length ; one circumscribed mural adhe- 
sion. Distal thrombus, none. Ligatures completely encysted in a 
spindle-shaped, fibrous capsule inclosing the intervening portion. 
Circular intravascular cicatrix underneath the peripheral ligature. 
Intervening portion patent. The inner tunics are not ruptured. 
Experiment No. 8.-Right carotid ligated with coarse catgut. 
Animal killed 12 days after operation. Ligatures and intervening 
portion surrounded by a fibrous capsule. Proximal thrombus coni- 
cal, and nearly one inch in length. Circumscribed points of adhe- 87 
sion near ligature. No peripheral clot. Circular cicatrix closing 
the vessel completely and firmly underneath the distal ligature. 
Intervening portion patent. 
Experiment No. 9.-Right femoral artery ligated with medium- 
sized silk ligatures. Animal killed 13 days after operation. A large 
abscess communicated with the seat of the operation, the walls of 
the abscess surrounding both ends of the vessel. The intervening 
portion is much shrunken and completely necrosed and separated. 
Both ends of artery firmly closed. The proximal end contained 
a very small thrombus. The cicatricial tissue surrounding the 
artery had drawn the ends together so as to give the appearance as 
though the artery had suffered no loss of continuity. 
Experiment No. 10.-Left carotid tied with coarse catgut. Animal 
killed 14 days after operation. No thrombus. Ligatures and inter- 
vening portion surrounded by a firm, fibrous capsule. Ligatures 
completely encysted, but remaining quite firm. A firm, circular 
cicatrix completely obliterating the artery underneath the proximal 
ligature. Inner coats not injured. Walls of intervening portion 
much thickened, and its lumen near distal ligature much contracted. 
Experiment No. 11.-Right carotid tied with coarse catgut. 
Animal killed 15 days after operation. Proximal thrombus nearly 
3' in length, almost filling the lumen of the vessel, but non-adhe- 
rent. No distal thrombus. Ligatures and intervening portion of 
vessel completely encysted. Size of catgut unchanged. Inner 
tunics not injured. Obliterating circular cicatrix underneath distal 
ligature. Lumen of intervening portion diminished in size, and its 
walls thickened. 
Experiment No. 12.-Left carotid ligated with fine silk. Animal 
killed 18 days after operation. Small proximal thrombus. No dis- 
tal thrombus. The intervening portion and ligature completely 
encysted. Lumen of vessel immediately above the distal ligature 
closed by a firm cicatrix. Lumen of the intervening portion reduced 
in size. Folds of intima filled with granulation tissue. 
Experiment No. 13.-Subcutaneous artery of thigh of sheep 
ligated with medium sized catgut. Sheep killed 21 days after ope- 
ration. No thrombi. Ligatures and intervening portion surrounded 88 
by spindle-shaped mass of connective tissue. Lumen of interven- 
ing portion of vessel completely obliterated (Fig. 2). 
Fig- 2. 
Experiment No. 14.-Right common carotid ligated with fine 
catgut. Animal killed 21 days after operation. No thrombus. 
Intervening portion, ligatures, and pneumogastric nerve surrounded 
by a firm capsule of connective tissue. Lumen of intervening 
portion contracted and filled with granulation tissue, more near 
proximal ligature. Only the knot of the peripheral ligature remains. 
Firm union underneath the ligature. 
Experiment No. 15.-Left carotid tied with silkworm ligature. 
Animal killed 25 days after operation. No thrombus. Ligature 
unchanged and encysted. Coats of intervening portion of vessel 
thickened. Circular cicatrix underneath the proximal ligature, 
which has cut through the greater portion of the vessel-walls. Inter- 
vening portion permeable. Intima presents a roughened appearance. 
Experiment No. 15^2.-Right femoral tied with fine silk. Animal 
killed 35 days after operation. No thrombus. Ligatures encysted. 
A firm, fibrous mass between ligatures, in which the lumen of the 
artery, much reduced in size and nearly obliterated, could be iden- 
tified. Vessel pervious to points of ligation (Fig. 3). 
Fig- 3- 89 
Experiment No. 16.-Right carotid. Catgut ligature. Animal 
killed after 39 days. No thrombus. Ligatures encysted. Knots 
distinctly visible. Artery obliterated one-half inch above the peri- 
pheral ligature. Below, vessel pervious to near ligature. Transverse 
section between ligatures shows a mass of connective tissue in which 
the obliterated artery can be distinctly seen (Fig. 4). 
Fig. 4- 
Experiment No. 17.-Right femoral ligated with coarse silk 
Animal killed 49 days after operation. No thrombus. Ligatures 
encysted. Artery on either side of ligatures obliterated to a distance 
of one-sixth of an inch. Section between ligatures reveals the 
vessel in a mass of cicatricial tissue, somewhat reduced in size, its 
lumen filled with a mass of organized tissue (Fig. 5). 
Fig- 5- 
Experiment No. 18.-Left femoral tied with coarse braided silk. 
Distal ligature just above profunda. Animal killed 50 days after 
operation. No thrombus. Ligatures encysted. On the proximal 
end the artery is obliterated to a distance of one-eighth of an inch 
above ligature. Intervening portion converted into a solid string of 90 
connective tissue in which the remains of the artery can still be 
recognized (Fig. 6). 
Fig. 6. 
Experiment No. 19.-Right femoral; medium-sized catgut. 
Animal killed after 52 days. No thrombus. Artery pervious to 
ligatures. No traces of the ligatures can be found. Intervening 
portion of vessel and vagus surrounded by a spindle-shaped mass 
of connective tissue in which no distinct traces of the vessel can 
be found (Fig. 7). 
Fig. 7- 
Experiment No. 20.-Right femoral; silkwormgut ligature. 
Animal killed 55 days after operation. No thrombus. On proximal 
side vessel obliterated to a distance of one-third of an inch ; below, 
three-fourths of an inch from the ligature. Ligatures have appa- 
rently cut through the vessel, and are completely encysted. Inter- 
vening portion surrounded by a large mass of connective tissue in 
which the closed lumen of the vessel can plainly be seen. 
Experiment No. 21.-Right femoral. Medium-sized silk, distal 
ligature just above profunda. Animal killed after 68 days. Pro- 
funda converted into a fibrous cord. In the deep femoral remnants 91 
of a thrombus about one-half of an inch in length. Vessel oblite- 
rated to same distance. Ligatures cut through. One of them 
imbedded in a mass of cicatricial tissue in which the intervening 
portion of the vessel could not be recognized. A small abscess 
communicated with the seat of the operation through which one of 
the ligatures must have escaped. 
Experiment No. 22.-Left carotid of goat tied with catgut. 
Animal killed after 80 days. Proximal end of vessel obliterated 
to within the next collateral branch, one-third of an inch below 
ligature. Distal portion of artery obliterated to same extent, to 
within one-half of an inch of its bifurcation. Ligatures completely 
disappeared, and intervening portion converted into a solid string 
of connective tissue (Fig. 8). 
Fig. 8. 
Experiment No. 23.-Right femoral of goat tied with silk. 90 
days. Artery pervious to within one-half of an inch on each side 
of the ligatures. Ligatures probably cut through the vessel, and 
completely encysted. Intervening portion of vessel transformed 
into a solid mass of connective tissue about the size of the vessel. 
Experiments with the Double Temporary Ligature on Arteries. 
Experiment No. 24.-Right common carotid of goat tied with 
coarse catgut; removed 25 hours after operation. Animal killed 
10 days after ligation. At the time the ligatures were removed the 
circulation in the vessel was interrupted. On examination the artery 
and the vagus were found surrounded by a copious mass of cicatri- 
cial tissue. Interiorly, the vessel corresponding to the seat of the 
ligatures is filled and occluded by a small white thrombus project- 
ing into the distal portion of the vessel. Cicatricial tissue in lumen 
continuous with the para-vascular connective tissue. 92 
Experiment No. 25.-Left femoral of goat. Coarse catgut. 
Removal 24 hours after operation. Animal killed 9 days after liga- 
tion. On removal of ligatures circulation not interrupted. Ligated 
portion of vessel considerably smaller. Lumen not obliterated. 
Inner walls of vessel at the seat of operation studded with minute 
patches of exudation material, the result of recent endarteritis. 
Experiment No. 26.-Left carotid. Coarse catgut; removed 48 
hours after operation. Animal killed 10 days after ligation. On 
removal of ligatures circulation in vessel not interrupted. An 
abscess with thick walls communicates with the vessel. The vessel 
surrounded by a thick fibrous capsule. No thrombus. Lumen of 
vessel between seat of ligatures narrowed by a copious plastic exu- 
dation on that part of the vessel which is in immediate contact with 
the abscess. 
Experiment No. 27.-Left carotid. Silk ligature; removed 48 
hours after operation. Animal killed 14 days after operation. Cir- 
culation not interrupted. Post-mortem appearances the same as in 
No. 25. 
Experiment No. 28.-Left carotid. Silk ligature ; removed 72 
hours after operation. Animal killed 35 days after operation. Cir- 
culation, on removal of ligatures, interrupted. Proximal clot 1^ 
inch in length with circumscribed points of adhesion. Distal clot 
none. At seat of operation vessel very much contracted. Lumen 
filled with remnants of a small clot and granulation tissue. 
Experiment No. 29.-Left carotid. Silk ligature ; removed after 
72 hours. Animal killed 35 days after operation. Circulation inter- 
rupted. Suppuration followed the removal of the ligatures. Proxi- 
mal thrombus about 2' in length. Coats of vessel very much 
thickened. Thrombus adherent by plastic exudation from inner 
vessel-walls. Distal thrombus very minute. Intervening portion 
separated at one end, projecting into the abscess cavity. Both ends 
of the artery permanently obliterated, united, and brought into 
close approximation by a mass of cicatricial tissue. 
Experiment No. 30.-Right carotid. Silk ligature; removed 72 
hours after operation. Animal killed 28 days after ligation. 
Removal of ligatures followed by suppuration. No thrombi. 93 
Both ends of the vessel permanently obliterated and brought into 
close contact by a mass of cicatricial tissue in which no trace of the 
intervening portion can be found. Ligated portion of vessel has 
probably sloughed, and escaped with the contents of the abscess 
which communicates with the seat of the operation. 
Experiment No. 31.-Right common carotid near subclavian. 
Coarse catgut. Ligatures removed 6 days after ligation. Animal 
killed 16 days after operation. Circulation completely arrested on 
removal of ligatures. No thrombi. Vessel, at seat of ligatures, 
surrounded by spindle-shaped mass of connective tissue, in a trans- 
verse section of which the artery can be readily identified, its lumen 
being filled with embryonal connective tissue (Fig. 9). 
Fig- 9- 
Experiment No. 32.-Left common carotid. Coarse catgut. 
Ligatures removed 6 days after operation. Animal killed 14 days 
after ligation. On removing distal ligature vessel gave away. No 
hemorrhage. Distal end closed by a narrow cicatrix. Very minute 
thrombus. Thrombus in proximal end 2' in length ; firmly adhe- 
rent. At point of proximal ligature narrow circular cicatrix. Inter- 
vening portion of vessel separated at one end. Not necrosed. Both 
ends of vessel connected by a strong bridge of connective tissue. 
Double Ligation of Veins. 
Experiment No. 33.-Right jugular. Catgut ligature. Animal 
killed six hours after operation. Minute peripheral thrombus. In- 
creased vascularity of adventitia. 94 
Experiment No. 34.-Left femoral vein. Catgut ligature. Animal 
killed after 24 hours. Filiform distal thrombus ; none on the proxi- 
mal side. Intervening portion completely empty, and slightly ad- 
herent to surrounding tissues. 
Experiment No. 35.-Right femoral vein. Coarse catgut ligature. 
Animal killed after 3 days. Small distal thrombus. Intervening 
portion adherent to surrounding tissues, and containing in its interior 
a small granulation thrombus 
Experiment No. 36.-Right jugular vein. Coarse catgut ligature. 
Animal killed after 5 days. Minute distal thrombus in folds of 
intima. On removing proximal ligature the inner surfaces of in- 
tima were found firmly adherent, evidently by direct union. 
Experiment No. -Right femoral. Coarse silk ligature. 7 days. 
Suppuration after operation. Minute peripheral clot. Ligatures 
encysted. Intervening portion partially destroyed by suppuration. 
Ends of vessel united by a bridge of connective tissue. Vessel 
underneath the ligatures obliterated. 
Experiment No. 38.-Right jugular vein. Silk ligature. Animal 
killed after 9 days. Suppuration followed the operation. Abscess 
communicated directly with the intervening portion of the vessel 
which has nearly separated. Small truncated distal thrombus, non- 
adherent. Ends of vessel firmly closed and united by a strong 
bridge of connective tissue. 
Experiment No. 39.-Right jugular vein. Medium sized silk 
ligature. 12 days. Minute adherent distal thrombus. Ligatures 
encysted. Intervening portion surrounded by a capsule of connec- 
tive tissue. On transverse section the star-shaped lumen of vessel 
is discernible, firmly closed by young connective tissue (Fig. 10). 
Fig. io. 95 
Experiment No. 40.-Left jugular vein. Silk ligature. Animal 
killed after 14 days. No thrombi. Ligatures encysted. In re- 
moving the proximal ligature firm adhesions between folds of intima. 
Intervening portion empty, and adherent to surrounding tissues. 
Experiment No. 41.-Right jugular vein. Horse hair ligatures. 
21 days. No thrombi. Ligatures not encysted, loose upon the 
remaining parts of the intervening portion. Ends of vessel closed 
by very narrow cicatrix. 
Experiment No. 42.-Right jugular vein. Catgut ligature. 37 
days. Ligatures encysted. Vessel obliterated to a distance half an 
inch from ligatures on both sides. Intervening portion a solid string 
of connective tissue in which no traces of the vessel can be found 
(Fig- ii)- 
Fig. ii. 
I 
Experiment No. 43.-Right jugular vein. Coarse silk ligature. 
49 days. Vessel pervious to near ligatures. Ligatures encysted. 
Intervening portion surrounded by a mass of connective tissue in 
which the obliterated vessel can be readily identified (Big. 12). 
Fig. 12. 
Experiment No. 44.-Right femoral vein. Medium-sized silk 
ligature. 54 days. Vessel pervious to near ligatures. Ligatures 96 
evidently have cut their way through the vein and are encysted in 
the cicatrix. Intervening portion transformed into connective 
tissue (Fig. 13). 
Fig- 13- 
Experiment No. 45.-Right jugular. Medium-sized catgut. 80 
days. Ligatures absorbed. Intervening portion transformed into 
connective tissue. 
Experiments with the Double Temporary Ligature on Veins 
Experiment No. 46.-Right jugular of goat. Silk ligature, re- 
moved 24 hours after operation. Animal killed 10 days after 
operation. Circulation on removing ligatures not arrested. Inter- 
vening portion contracted by a mass of intramural and para-vascular 
cicatricial tissue, but patent. Intima normal in appearance An 
abscess communicates with the seat of the operation, only the coats 
of the vein intervening between it and the lumen of the vessel. 
Experiment No. 47.-Left jugular vein. Silk ligature, removed 
48 hours after operation. Animal killed 34 da\s after ligation. 
Circulation arrested. No thrombi. Intervening portion of vessel 
transformed into a firm string of connective tissue, in which no 
trace of the original structure can be recognized (Fig. 14). 
Fig- 14- 
Experiment No. 48.-Right jugular. Silk ligature, removed 3 
days after operation. Animal killed 27 days after ligation. Circu- 97 
lation arrested at seat of ligatures. Peripheral clot narrow, partially 
adherent, one inch in length At the seat of operation about 2' of 
the vessel converted into a solid string of connective tissue (Fig. 15). 
Fig- *5- 
Experiment No. 49.-Left jugular. Coarse silk ligature, removed 
3 days after operation. Animal killed 40 days after ligation. Cir- 
culation interrupted. No thrombi. Intervening portion converted 
into a massive string of connective tissue (Fig. 16). 
Fig. 16. 
Experiment No. 50.-Left jugular. Coarse silk ligature removed 
4 days after operation. Animal killed 35 days after ligation. Cir- 
culation interrupted. A short truncated peripheral clot adherent 
at its base. Constricted portion of vessel almost but not completely 
obliterated. Folds of intima filled with recent connective tissue, 
bridges of same material spanning the lumen of the vessel. The 
surface of the intima corresponding to the wound covered by a 
copious plastic exudation. 
Experiment No. 51.-Right jugular. Coarse catgut ligature, re- 
moved after 6 days Animal killed 15 days after the operation. 
Suppuration followed the operation. Circulation arrested. An 
immense white peripheral thrombus adherent at its base. Vessel at 98 
seat of distal ligature obliterated by a narrow cicatrix. Intervening 
portion contracted, walls thickened, circumscribed patches of exuda- 
tion underneath the proximal ligature. 
Experiment No. 52.-Right jugular. Coarse catgut, removed 
after 6 days. Animal killed 14 days after operation. Vein com 
pletely obliterated at points of ligation. Intervening portion sur- 
rounded by a dense capsule of connective tissue, a transverse section 
of which shows the lumen of the vessel almost completely obliterated 
by plastic exudation. 
Experiments on a Horse. 
Experiment No. 53.-Right carotid. Silk ligatures. Animal 
died 8 days after operation, death being caused by chloroform 
during the second experiment. Proximal clot extending to near 
subclavian, partly adherent, distal clot 8' in length, extending be- 
yond nearest collateral branch. Ligatures encysted. Intervening 
portion surrounded by a capsule of connective tissue. Walls thick- 
ened. Beginning cicatrization under peripheral ligature. 
Experiment No. 54 -Right jugular vein of same animal. Coarse 
silk ligature. 8 days. Large distal thrombus completely distend- 
ing the vein, and extending beyond bifurcation. Ligatures en- 
cysted. Proximal portion of vein diminished in size. Intervening 
portion surrounded by a capsule of connective tissue. Underneath 
proximal ligature firm adhesions between folds of intima. 
XXIII. Remarks. 
A. Effect of Suppuration.-The deleterious influence of sup- 
puration on the process of cicatrization is well illustrated by these 
experiments. In all cases where the wound healed by primary 
union, the isolated portion of the vessel became adherent as early 
as the second day to the adjacent tissues, and, after a few days 
more, the interrupted vascular connections were restored. In 
all cases, with the exception of Experiments Nos. 9, 21, 37, 38, 
where the wound was not reopened for the purpose of removing 
the ligatures, the wound healed by primary union, and cicatriza- 
tion in the vessel progressed in a favorable manner. In using 99 
the temporary ligatures suppuration was a more frequent con- 
comitant on account of the necessary interference with the 
reparative process in the wound, and the increased difficulties 
encountered in preventing infection. Suppuration supervened 
in Experiments Nos. 26, 29, 30, 50, with the temporary ligature, 
so that this event occurred 8 times out of 55, the whole number 
of experiments. In all cases where suppuration followed the 
operation the vitality of the intervening portion of the vessel 
was destroyed in part or in its entirety, and if a sufficient length 
of time had elapsed, this portion of the vessel was usually found 
completely separated and within the abscess cavity. Secondary 
hemorrhage, however, was never observed as the result of sup- 
puration, or sloughing of the intervening portion, as the narrow 
intra-vascular cicatrix in both ends of the vessel was usually 
supported by a strong para-vascular ring of connective tissue 
which formed a part of the thick walls of the abscess. In all 
these cases the vessels had invariably suffered a loss of continuity 
by the ligature. These facts force upon us the following con- 
clusions :- 
1. All surgical operations on bloodvessels should be performed 
under strict antiseptic precautions for the purpose of preventing 
suppuration. 
2. In aseptic wounds the complete isolation of a vessel from 
its sheath for a distance of one inch is not followed by any serious 
disturbance of nutrition in the vessel-walls. 
3. Suppuration invariably produces a loss of continuity of the 
vessel at the seat of ligature. 
4. Inflammation beyond the limits of the reparative process 
interferes with the typical formation of the intra-vascular cicatrix. 
B. Thrombus.-For nearly fifty years the idea has prevailed, 
and to a great extent is still prevalent, that in applying a ligature 
to an artery a thrombus forms on the proximal side which ex- 
tends to the nearest collateral branch, and that by organization of 
the clot the vessel is obliterated to the same extent. All authors 
who attribute definitive vessel closure to organization of a throm- 
bus assert that the latter always precedes cicatrization, and when 
thrombus formation fails to take place, permanent obliteration 100 
of the ligated vessel is an impossible occurrence. I have shown 
elsewhere that thrombosis by no means necessarily follows every 
case of ligation, in fact that it very often fails to take place, and yet 
definitive closure takes place as promptly as though a thrombus 
had formed. Coagulation of the blood means necrosis or death 
of the morphological elements of the clot, and as such an occur- 
rence it is more likely to result from conditions unfavorable to 
the process of cicatrization. Severe traumatic injuries of the 
vessel and, more particularly, an infectious inflammation of the 
seat of operation, are conditions which favor the formation of a 
thrombus. In my experiments on arteries I find that in 34 
cases the presence of a proximal thrombus is mentioned 13 times 
to 10 in the distal portion of the artery. In four of the experi- 
ments it is noted that only a peripheral thrombus formed in 
seven cases in which the thrombus was only found on the proxi- 
mal side of the ligature. In most of the cases the thrombus was 
quite minute, only seldom filling the entire lumen of the vessel, 
and never adherent to the entire inner surface of the vessel. A 
notable exception was furnished by the experiment on a horse, 
where an immense proximal and distal thrombus formed, filling 
the entire lumen of the vessel, extending on the proximal side 
near to the subclavian artery, and on the peripheral to beyond 
the bifurcation of the vessel. 
In the specimens derived from 21 experiments on veins I 
was never able to find even a trace of a thrombus on the 
proximal side of the ligature, while the presence of a distal 
thrombus is noted eleven times or a little more than fifty per 
cent, of all the cases. The vein experiments furnished the 
most favorable opportunities to study the process of cicatri- 
zation underneath the proximal ligature independently of a 
thrombus, as the presence of a clot was excluded in every 
instance. With the exception of the specimen obtained from 
the horse, the thrombi in veins were also usually small in size, 
and seldom adherent over any considerable surface. Only in 
exceptional cases, both in arteries and veins, did the thrombus 
reach as far as the nearest collateral branch. The results of 
these experiments render it obvious that the time-worn rule laid 101 
down in most of our text-books on surgery, which directs the 
operator to apply the ligature in such a manner as to leave a 
space of one inch or more between the ligature and the nearest 
proximal collateral branch for the purpose of insuring the for- 
mation of a thrombus, is wrong, both in theory and in practice, 
and should no longer be followed as a guide in deciding upon 
the seat of ligature. 
C. Ligature.-All ligatures were made strictly aseptic, and in 
all instances where suppuration did not follow the operation 
they were encysted irrespective of the material used. Silk, 
silkwormgut, and horsehair were not affected by the granulating 
process, but were always found unchanged in the cyst. In all 
aseptic wounds the loop of the ligature was found covered 
completely by the swollen adventitia after the first forty-eight 
hours. A great contrast was observed between the catgut 
ligature and ligatures made of material not susceptible to 
absorption as far as their effect on the vessel-walls was con- 
cerned. Catgut applied itself easily and smoothly to the 
exterior of the vessel-walls, and by becoming softened and 
infiltrated with cells, it appeared to constitute a part and parcel 
of vessel-tissues until it was replaced by substitution by a ring 
of organized tissue, which served as a material support to the 
vessel until cicatrization was completed, thus preserving the 
continuity of the vessel. All the remaining kinds of ligatures 
appeared to act as foreign bodies as far as the vessel tunics 
were concerned, and invariably produced a solution of con- 
tinuity after a sufficient length of time had elapsed. They 
were usually found encysted in the mass of connective tissue 
between, and some distance from, the ends of the vessel. Cat- 
gut, on the other hand, did not manifest this tendency. It 
became encysted, and underwent absorption in situ. The 
earliest time in which the catgut ligature was found absorbed 
was twenty-one days, in Experiment No. 14, where only the 
knot remained. In Experiment No. 19, where fifty-two days 
had elapsed after the operation, no trace of the ligature could 
be found. For the following obvious reasons, catgut recom- 
mended itself as the most desirable and efficient material:- 102 
I. If catgut is well prepared it will resist absorption until 
definitive obliteration of the vessel has taken place. 
2. It does not act as a foreign body, and does not destroy 
the continuity of the vessel. 
3. It is completely absorbed and replaced by organized tissue, 
which furnishes an additional support to the vessel-walls at the 
seat of cicatrization. 
D. Extra-vasczilar Cicatrix.-The first attempt at obliteration 
of a bloodvessel after ligature is manifested in the connective 
tissue of the adventitia and the para-vascular connective tissue. 
As early as twenty-four hours after ligation, the isolated portion 
of the vessel has become adherent to the surrounding tissues, 
and the swollen adventitia overlaps and covers the loop of the 
ligature. The connective tissue becomes very vascular, and 
undergoes rapid embryonal transformation, being converted in 
a few days into granulation tissue which completely surrounds 
and embraces the ligatures, the intervening portion, and the 
vessel ends in a similar manner as the provisional callus incloses 
the ends of a fractured bone. This capsule of connective tissue 
was always found present in every specimen, and in many 
instances was of remarkable size and strength. The thickest 
portion of the capsule always corresponded to the locality which 
had been subjected to the greatest amount of traumatism, that 
is, the side of the vessel towards the operation wound. As 
soon as definitive closure of the vessel has taken place, the 
capsule diminishes in size, until after a period of three months 
it did not exceed the original diameter of the ligatured vessel. 
The contraction incident to all cicatricial tissue manifests itself 
also in the spindle-shaped mass of connective tissue which forms 
around vessels after ligation, and renders material assistance in 
the process of obliteration by compressing the vessel, thus 
diminishing its lumen. In all of our experiments where union 
of the operation wound occurred without suppuration, the inter- 
vening portion of the vessel was found covered by granulation 
tissue as early as the third day, and the fibrous capsule was always 
firmly adherent to it. Through the medium of this connective- 
tissue capsule the ligated ends of the vessel always form firm 103 
adhesions with the surrounding structures, the artery, vein, and 
nerve often being enveloped by one common capsule, as may 
be seen well illustrated by Fig. 4. 
E. Intra-vascular Cicatrix.-By continuity the inflammatory 
tissue production proceeds from the adventitia in a central direc- 
tion towards the lumen of the vessel until the connective-tissue 
proliferation perforates the endothelial lining of the intima, an 
event which initiates the formation of the intra-vascular cicatrix. 
Simultaneous with the appearance of the granulation process in 
the intima and the appearance of new vessels from the adven- 
titia the endothelial cells assume an active part in the process of 
cicatrization, the new tissue elements mingling with the connec- 
tive-tissue product and assisting the same in the formation of 
the internal or definitive cicatrix. Cicatrization begins always 
underneath and in the immediate vicinity of the ligature. This 
fact receives a satisfactory explanation by assuming that the 
greatest amount of traumatism is inflicted at this point, and that 
by interrupting the circulation in the vasa vasorum by the liga- 
ture an active engorgement is produced which accelerates tissue 
changes and the formation of new vessels, at the same time the 
inner surfaces of the intima are here brought into accurate and 
uninterrupted contact. In my experiments on arteries three days 
was the shortest period of time in which a narrow firm cicatrix 
formed underneath the proximal ligature (Exp. No. 3). In the 
experiments on veins the condition of the vessel was always 
examined underneath the proximal ligature, inasmuch as any 
changes in the tunics and lumen of the vessel at this point had 
to be attributed to the tissues themselves independently of a 
bloodclot, as the intervening portion was always made bloodless 
and a thrombus was never found on the proximal side of the 
ligature. In the specimen derived from Experiment No. 36 I 
found a firm circular cicatrix underneath the ligature on the 
fifth day. The intervening portion of the vessel was carefully 
examined at times ranging from six hours to ninety days after the 
operation. This portion of the vessel, although deprived of all 
vascular supply, never necrosed unless suppuration followed the 
operation. Nutrition was sustained by plasma derived from 104 
para-vascular tissues until the interrupted circulation in the vasa 
vasorum was established, when the vessel tunics were again 
brought into a condition capable of entering into active tissue 
proliferation. In many of the specimens it is noted that the 
walls of the intervening portion were found thickened, which 
would certainly indicate that the tissues did not remain in a 
passive condition but were actively engaged in the work of 
tissue proliferation. The earliest time at which granulation 
tissue was found upon the free surface of the intima was seven 
days in the case of arteries (Experiment No. 4), and three days 
in the case of veins (Experiment No. 35). The formation of 
the cicatrix in the lumen of the vessel always began near the 
ligatures, the material filling the folds of the intima often form- 
ing distinct bridges connecting the highest points of adjacent 
ridges. In several instances I observed the greatest amount of 
exudative tissue on that surface of the vessel which was directed 
towards the wound. The amount of granulation material in 
the lumen of the vessel appeared to vary; in some specimens 
the lumen presents a stellate shape, the surfaces of the intima 
adherent with a minimum amount of material between them 
(Fig. 10), while in other specimens a cylindrical mass of embry- 
onal connective tissue occupies the interior of the vessel (Fig. 5). 
Complete obliteration of the intervening portion took place in 
the femoral artery 35 days after operation (Experiment No. 151), 
in 39 days in the carotid (Experiment No. 16), and in 12 days 
in the jugular vein (Experiment No. 39). As cicatrization ad- 
vances the original structures of the tunics disappear, the cndo- 
thelia are transformed into connective tissue, and between the 
para-vascular and intra-vascular cicatrix the elastic and muscular 
tissues undergo degeneration and are removed by absorption- 
The ultimate effects of the ligature are obliteration of the lumen 
and conversion of all the tunics of the vessel into a solid string 
of connective tissue which is again destined to undergo various 
degrees of atrophy. 
F. Temporary Ligature.-The experiments with the tempo- 
rary ligature were made with a view to ascertain intra vitam, 
the time required for definitive closure to take place after liga- 105 
tion. In arteries where the ligatures were removed 24 and 25 
hours after ligation, and the animals killed on the 10th and 9th 
days, no definitive closure had taken place, but the specimens 
presented evidences of arteritis and endarteritis. In Experiment 
No. 29 the carotid artery was ligated and the ligatures were 
removed 72 hours after operation, when the circulation was 
found completely interrupted; and the specimen obtained 35 
days after operation showed that the vessel had been completely 
divided by one of the ligatures, but both ends were permanently 
obliterated. In Experiment No. 31 (carotid artery) the ligatures 
were removed after 6 days, and the specimen obtained 16 days 
after operation showed that the intervening portion was under- 
going definitive obliteration, its contracted lumen being filled 
with a small granular thrombus (Fig. 9). 
In the veins the temporary ligature appeared to produce its 
effects in a shorter time and with a greater degree of certainty. 
In two experiments on the jugular vein (Experiments Nos. 47 
and 48) the ligatures were removed after 48 hours, and in both 
cases the circulation was completely and permanently arrested; 
and the specimens obtained 34 and 27 days after operation 
showed that the intervening portions had been converted into 
strings of connective tissue (Figs. 14 and 15). 
From these experiments it appears that in arteries the size of 
the carotid at least three days are required for the cicatrix 
underneath the ligature to become sufficiently firm to resist the 
intra-arterial pressure independently of the ligature, while in 
the jugular vein the same object is accomplished in two days. 
G. Microscopical Appearances of the Recent Intra-vascular Cica- 
trix.-I shall not attempt to give a detailed account of the micro- 
scopical appearances of the different tunics at different and succes- 
sive stages during the process of cicatrization, but I shall limit 
my remarks to a short description of the embryonal tissues which 
are found within the lumen of the intervening portion of the 
vessel and its immediate boundaries. These observations were 
made on transverse sections through the intervening portion 
equidistant from the ligatures. Figure 17 represents the inner 
border of the wall of the femoral artery and a portion of its 106 
lumen in a transverse section of the specimen obtained from 
Experiment No. 19, 52 days after operation. The open lumen 
of a small vessel can be seen in the intima near its inner border, 
brom the intima projections of connective-tissue proliferation 
Partly formed connective 
Vasavasorum. Intima. tissue from endothelia. 
Fig. 17. 
Proliferated 
connective 
tissue in 
lumen. 
Endothelial 
proliferation. 
Microscopical appearances presented by specimen from Experiment No. 19. Fig. 7. 
Transverse section through border, artery. X 240. 
are seen to penetrate into the lumen of the vessel, pushing before 
them the endothelial lining, and perforating it at different points, 
forming subsequently a network of connective tissue in the in- 
terior of the vessel, in the meshes of which are seen masses or 
nests of new endothelial cells, also products of the pre-existing 
endothelial elements. At certain places the endothelial cells 
assume an oval and spindle-shaped form prior to their being 
transformed into connective tissue. Bloodvessels from the 
intima accompany the projections of connective tissue into the 
lumen of the vessel. 107 
Figure 18 represents a transverse section through the inter- 
vening portion of the jugular vein obtained 49 days after opera- 
tion from Experiment No. 43, and illustrated by Fig. 12. It 
shows the intima and a portion of the granulation thrombus 
Fig. 18. 
Young 
corrective 
tissue 
cells. 
Proliferation 
of connective 
tissue. 
Endothelial 
proliferation 
Connective 
tissue of 
vein wall. 
Microscopical appearances presented by specimen from Experiment No. 43. Fig. 12. 
Transverse section of part of vein in ligated portion. X 240. 
which has permanently closed the lumen of the vessel. The 
microscopical appearances are almost identical with the arterial 
specimen. Both of these illustrations furnish the best possible 
demonstration of the manner in which the intra-vascular cicatrix 
is formed from the connective tissue and endothelia. The ma- 
croscopical and microscopical examination of the specimens are 
alike confirmatory of the assertion that the intra-vascular cicatrix 
is the exclusive product of connective tissue and endothelial 
proliferation. 108 
XXIV. Practical Suggestions. 
o o 
The results of my own experiments, as well as the literature 
on the subject, tend to prove that all kinds of ligatures, provided 
they have been made aseptic, always become encysted in aseptic 
wounds. All ligatures, however, which permanently resist ab- 
sorption destroy the continuity of the vessel, and on this account, 
instead of adding strength to the para-vascular cicatrix, weaken 
the vessel-walls at the seat of ligation. I have never observed 
a single case in hospital or private practice where the catgut 
ligature failed to fulfil in the most satisfactory manner the 
purposes of a provisional haemostatic agent until the definitive 
cicatrix had become sufficiently firm to resist the intra-arterial 
pressure. In place of severing the tunics of the ligated vessel 
the catgut ligature is gradually displaced by organized tissue 
which increases the resisting capacity of the vessel, providing 
an additional safeguard against secondary hemorrhage if from 
any cause definitive obliteration is retarded. In enumerating 
the superior advantages of the catgut ligature, Nussbaum says : 
"The most careful microscopical examinations have shown that 
catgut increases to a considerable extent the resisting capacity 
of an artery in forming firm connective-tissue connections with 
the vessel."1 
The aseptic animal ligature possesses two distinct and im- 
portant advantages over all permanent ligatures. I. It does not 
necessarily destroy the continuity of the vessel. 2. It adds addi- 
tional strength to the extra-vascular cicatrix. These advantages 
recommend the animal ligature more particularly for the purpose 
of tying a vessel in its continuity. I am firmly convinced that 
in many of my experiments the internal tunics of the arteries 
remained intact after ligation, and yet cicatrization progressed 
in a satisfactory manner. Hence it is no longer necessary to 
tie the ligature so firmly as to crush the tunics of the vessel. 
All that is necessary is to tie with sufficient force to approximate 
the inner surfaces of the intima with a view to insure effective 
1 Op. cit. 109 
provisional obliteration of the vessel when cicatrization will fol- 
low as a necessary result, provided the vessel tunics are in a 
healthy condition. If cicatrization in a vessel takes place from 
the fixed cells of its tunics without the formation of a thrombus, 
it will be seen that in many instances a vessel can be ligated 
with safety in its continuity close to a collateral branch when 
existing circumstances dictate such a course. 
One of the constant rules usually given by all authors in vessel 
surgery was to make a small opening in the sheath of the 
vessel, only of sufficient size to permit of passing the ligature 
needle around it. It was feared that a more free opening in the 
sheath, and a more extensive isolation of the vessel would lead 
to necrosis of its tunics on account of the cutting off of the vas- 
cular supply. That this idea still prevails is evident from one of 
the most recent text-books on surgery. Lidell calls special atten- 
tion to this point in the following language: "The risk of slough- 
ing, howrever, arises mainly from isolating the artery too much, 
or from separating it too extensively from its sheath, while dis- 
secting to expose it, or while preparing to pass a thread around 
it whereby the minute vessels which nourish its coats are too 
extensively destroyed; hence the dangerousness of passing a 
spatula or the handle of a scalpel under the artery, and of dragging 
it out of its bed when tying it."1 
All of these fears are unfounded when operating under anti- 
septic precautions. In all of my experiments I did all what is 
here cautioned against: I isolated the arteries and veins from 
their sheaths for an inch or more, and dragged the vessel near 
to the surface of the wound in applying the second ligature, 
and yet I never observed any sloughing except in the cases 
where the operation was followed by suppuration. I am strongly 
in favor of opening the sheath freely, so that the operator can 
not only feel but see what he is doing, and I am convinced by 
pursuing this course there is less harm done than by operating 
in the dark. My experiments on the veins have taught me 
1 Injuries of Bloodvessels. The International Encyclop. of Surgery, vol. iii. 
p. 90. 110 
another important and practical lesson, viz., their tolerance to 
traumatic insults. In not one of the cases was death produced by 
the operation, although in a few of the animals both the jugular 
and femoral veins were tied at different times. I never observed 
progressive phlebitis, embolism, or pyaemia. Veins, like those 
of the peritoneum, may be contused, torn, lacerated, cut, punc- 
tured, burned, and ligated with immunity, if infection is avoided. 
Veins are exceedingly prone to infection, but if infection can be 
prevented their injuries are repaired with wonderful rapidity. 
As regards the time required for definitive obliteration to take 
place, the results of the experiments would indicate that in the 
case of arteries of the size of the carotid or femoral from four to 
seven days are necessary, while in the jugular vein the same 
object is accomplished in three to four days. 
The double catgut ligature may be resorted to with advantage 
in the human subject in ligating large vessels in their continuity, 
more especially if the operation is done near a collateral branch 
as it approximates the inner surfaces over a larger area and thus 
furnishes a more extensive surface for cicatrization. The prac- 
ticability and utility of the double ligature is, however, rendered 
most apparent in the treatment of varicose veins. For many 
years I have successfully used the subcutaneous double catgut 
ligature in the treatment of varicocele. In operating on varicose 
veins of the lower extremity, the intervening portion can readily 
be rendered bloodless by applying an Esmarch's bandage before 
tying the ligatures. The entrance of blood into the vessel be- 
tween the ligatures through small collateral branches can be 
prevented, and the process of cicatrization materially assisted by 
applying an antiseptic compress over the seat of the operation 
before removing the elastic bandage. 
A careful examination of the literature on the subject of this 
paper, as well as the results of my own investigations, warrant 
me in submitting for your further consideration and discussion 
the following conclusions:- 
I. All operations on bloodvessels should be done under anti- 
septic precautions. 
II. The aseptic catgut ligature is the safest and most reliable 111 
agent in securing provisional and definitive closure of blood- 
vessels. 
III. A thrombus after ligature is an accidental formation 
which never undergoes organization and takes no active part in 
the obliteration of a vessel. 
IV. The intra-vascular or definitive cicatrix is the exclusive 
product of connective tissue and endothelial proliferation. 
V. Permanent obliteration in arteries takes place in from four 
to seven days, in veins in from three to four days. 
VI. In ligating vessels in aseptic wounds the vessel sheath 
can be opened freely without compromising the integrity of the 
vessel tunics, and such procedure renders the operation safer 
and easier of execution. 
VII. The double aseptic catgut ligature should be preferred 
to the single ligature in ligating large arteries in their continuity 
near a collateral branch, and should always be employed in all 
operations of tying varicose veins in their continuity as the 
safest and most effective measure in producing definitive oblit- 
eration. 
DISCUSSION. 
Dr. Donald Maclean, of Detroit, Michigan. 
It appears to me that it would be unjust for this Association to 
pass over Dr. Senn's paper without some observations. I certainly 
should not like to see it go without some comments. It is a long 
paper, and a pretty heavy task to listen to the whole of it at one 
time. But I am sure that I voice the opinion of every member of the 
Association, when I say that we feel proud of our brother after 
having listened to his production. It is an able, an ingenious, 
and a well-presented one in every respect, giving a number of most 
interesting and instructive experiments, with some very just deduc- 
tions from them. The fact of the matter is, it is a paper of a some- 
what revolutionary character. 
One point that struck me forcibly was the manner in which the 112 
author took the various very profound and apparently widely dif- 
ferent subjects of surgery, and led them all converging into one 
practical point. He speaks of ligature of the common femoral 
artery, a subject which was before us on the first day. The liga- 
ture of this artery for aneurism has been almost always condemned 
on account of the danger of secondary hemorrhage. The danger 
was, we believed, on account of the inability of the blood to coagu- 
late in the collateral branches. There was not space enough for a 
good solid clot to form between the ligature -and the collateral 
branches. Then, as far as aneurism is concerned, we can use the 
ligature if his reasoning is correct. But in wounds of the com- 
mon femoral, what shall we do? I have myself not met with a 
wound of the common femoral. To tie the common femoral for 
injury would be almost sure to stop the collateral circulation. But 
if Dr. Senn's conclusions are correct, and his deductions just, then 
we can lay that danger aside. If the aseptic ligature is used, and 
antiseptic principles are carried out, it cannot be necessary for a 
clot to form ; the artery is closed without the intervention of a clot. 
The paper is too vast and the subject too vast to admit of discus- 
sion here. I only wish for my own part to express my gratitude to 
Dr. Senn for having presented so able and remarkable a contribu- 
tion to the Association. 
Dr. Henry F. Campbell, of Augusta, Georgia. 
I arise to join Dr. Maclean in the hearty commendation he gives 
for the labor, the ingenuity, the deep research, and the very great 
importance of Dr. Senn's investigations. At the same time, I do 
not know that the American Surgical Association is prepared to 
let pass unchallenged in any manner some of his statements. I will 
not refer to the fact that a day or two ago we were discussing the 
question of ligation of the common femoral, and my own experience, 
as then stated, was that the danger was not from hemorrhage from 
the want of the formation of a clot, but that if you tie it for hemor- 
rhage in a healthy man, with the collateral vessels undilated as by 
an aneurism or inflammation, you certainly kill the man by the uni- 
versal stasis of the venous and arterial systems throughout the entire 
limb. That is my experience in three cases. But his experiments 
appear to rescue from neglect, from the apprehension, from the 
condemnation we have heretofore put upon it, the animal ligature 
for arresting an arterial current. It appears that the buckskin liga- 113 
ture was tried and abandoned for fear that it would not hold long 
enough. The deer-tendon ligature was suggested and tried. My 
predecessor in the Medical College of Georgia tried it, and had to 
abandon it because it did not hold the parts together long enough 
to form a well-organized clot. But since the days of Guthrie in the 
Crimea we have known that the coats of an artery unite like skin 
by adhesions. Therefore I am not willing to allow the utter con- 
demnation of the silk ligature. I have been using it for forty 
years, and I have had secondary hemorrhage only once. I sometimes 
think it well to violate Guthrie's rule and put on a double ligature, 
one above and one below the lesion. I have had hemorrhage- 
recurrent hemorrhage-from the lower end, and have been obliged 
to apply another silk ligature, but I have never had a hemorrhage 
from the brachial, the femoral, the carotid, or the posterior or ante- 
rior tibial arteries, that came from the application of any kind of 
ligature. I have never had an accumulation of pus surrounding the 
point of application of my- ligature. I never carbolize my silk. I 
wax it, and make it draw well into a knot, and I have never had 
any bad results in the ligation of any artery whatever. That there 
is sometimes retention of the knot, its slow coming away beyond the 
appointed time, according to the size of the artery, I must admit. 
You know, according to the class of the artery, many set a certain 
time for its closure, say ten days for the radial, twelve or fifteen for 
the brachial, fifteen or twenty for the carotid. I have had my liga- 
ture retained somewhat beyond this time. I have, however, never 
put a weight on it, but it has always come away after awhile. I 
know what retained it, it was the too active vitality in the part. The 
granulations crowded around my knot and my loop, and prevented 
it from coming away. Now if there was an accumulation of pus, I 
would have hesitated to apply that kind of a ligature; but it was 
the perfect ease, the perfectly fortunate results, that came from it. 
I rise merely to express my admiration for a gentleman who could 
make such research, and who has combined with his research a 
philosophical inductive study. He is able to concentrate and collate 
the principles of fact which make a perfect induction; but even the 
most perfect induction possible should never deny or obliterate from 
our memory the teachings of experience ; and it is simply that I may 
save the Association from giving itself without consideration to a 
new teaching that I have spoken. 114 
Dr. E. H. Gregory, of St. Louis, Missouri. 
I am perhaps an old fogy, for I am not prepared to abandon the 
silk ligature. I should put a ligature on the common femoral artery 
to-day with the same anxiety as I would have applied it yesterday; and 
whenever an opportunity offers to avoid a merely collateral branch 
in the ligation of an artery, I shall certainly do it. I would not 
subject my conscience to the discomfort it would occasion if I were 
to apply a ligature to an artery close to a collateral branch, unless I 
were obliged to do it, notwithstanding all that has been said on the 
subject. In other words, whilst I agree with the previous speaker, 
that Dr. Senn has done much, and that the paper which he has pre- 
sented is worthy of the American Surgical Association, and will, 
perhaps, add reputation to it, yet it is very hard for a man to change 
his practice. Within the last six weeks I tied at least six inches 
of the omentum with silk ligature, cut it off close, and returned 
the ends into the abdomen. And for my part I cannot see that 
there is any disadvantage attached to the use of the silk ligature. 
Now, my friend Dr. Campbell says that he finds that the growth 
of new tissue crowds and actually clamps his ligature; and I would 
add, that if it were permitted to remain there a few months it would 
disappear. This may seem strange to some of the Fellows, but I 
know that the silk ligature does disappear. I have removed it when 
the loop was half destroyed. Again, the author says that in a little 
while this ligature is infiltrated with a plasmic material. Now we 
know that this plasmic material is corroding, it is/consuming, it as- 
similates every structure with which it comes into contact. I am 
afraid that this animal ligature will not be capable of doing its 
duty. 
Perhaps I was too old when Listerism came into existence ; cer- 
tainly I have not become enthusiastic on the subject, and I do not 
know why I have not taken the contagion, because it has prevailed 
pretty generally. I have made operations with all these precautions, 
because I have an assistant who makes my preparations for me, and 
he attaches great importance to them. But I cannot attach the same 
importance to it that some men seem to attach to it. So that while 
I am willing to praise the paper of Dr. Senn, I feel like Sir Astley 
Cooper felt fifty years ago, when he put an animal ligature on an 
artery and had to put a silk one on afterwards. It is to-day just 
what it was then. 115 
Dr. J. S. Billings, United States Army. 
I wish to call the attention of the Association, as this subject of 
Listerism has come up, to the fact that it is to be judged not by indi- 
vidual experience, or what may have taken place in single instances, 
and, more still, not by the occurrences that take place in private 
practice. You must judge it by the results that follow its use in the 
old, badly ventilated, badly arranged, and unclean hospitals of 
Europe, and I think the best results may be seen in the hospitals 
of St. Petersburg, where, before the introduction of Listerism, the 
amputation of even a finger was a serious question, and the surgeons 
were in despair. Now the sanitary condition of these hospitals 
has not changed. They are still filled with the same filthy, miserable 
class of patients, but they perform the surgical operations without 
any fear of erysipelas or other complication. This also is the case 
I might remark of all the hospitals of Germany. 
It is not at all a fair thing to contrast a silk ligature with an animal 
ligature, for the silk is an animal ligature. It is only a little better 
kind of animal ligature. I am satisfied that you can get a good 
catgut ligature. Not everything that is called catgut is good ; but 
there is a catgut that is as satisfactory as the silk, and the facts 
stated about the absorption of silk ligature, the fact that it can be 
returned into the abdomen, I interpret to mean that it is an aseptic 
ligature. 
• 
Dr. B. A. Watson, of Jersey City, New Jersey. 
I desire to commend this most excellent paper. It is one of the 
most valuable productions I think that has ever been brought before 
this Association. As a scientific production alone it is worthy of 
our admiration. Then when we consider that the author experi- 
mented upon fifty-five animals, ligating arteries, and that in no single 
instance did he have septic trouble or secondary hemorrhage, and 
that in every instance where he used what he called the permanent 
ligature, he cut short the ends, placed the arteries back in their 
position, and even hermetically sealed and closed up the wound, 
the good results seem to me laudable. 
I have been in the habit of using catgut ligatures for the last ten 
years, and feel as much confidence in them as Dr. Gregory does in 
silk. I feel that one of the greatest dangers in ligation is from 
secondary hemorrhage ; and in the majority of cases it comes on 
from suppuration. If you can avoid suppuration in a wound, I 116 
think you will generally avoid secondary hemorrhage. With the 
carbolized ligature properly applied you avoid it; and I have not 
seen a case in which the catgut ligature, so applied, did not hold 
a sufficiently long time for the artery to be united and to give 
satisfactory results. 
Dr. C. B. Nancrede, of Philadelphia, Pennsylvania. 
I would like to call attention to one fact. I have been much 
interested in experiments on animals, yet I think that we should be 
careful about applying the results obtained from experiments on 
animals to similar cases in the human subject. You can open a 
dog's abdomen and sew it up again with no bad effects, but'you 
cannot do the same in a man and not have bad results follow. 
Now, as to catgut ligature, I think surely men like Billroth, Sir 
James Paget, and many other foreign surgeons know as much as 
we do. Now, the best result obtained from animal ligature was 
39 per cent., while that from silk ligature was only per cent. 
As to catgut ligature, if you get the right kind, I cannot conceive 
of the slightest danger in using it. I think we must have used it 
in hundreds of amputations in Philadelphia, and we seldom heard 
of hemorrhage following its application. I have made between 
sixty and seventy amputations, and I have never used anything but 
catgut, unless at night, when the material gave out. I cannot con- 
ceive why American surgeons believe in placing experience in a 
few cases against the best experiences abroad. Certainly, if you 
take the best results under certain circumstances, you eliminate the 
great cause of danger in others. The last volume of Transactions 
of our Society was treated with something very much like ridicule 
by foreign surgeons, inasmuch as American surgeons, they said, 
instead of relying on the experiences of the best men of the world, 
have relied on their own. 
Dr. Senn. In the first place, I desire to thank most sincerely the 
Fellows for listening so patiently to my paper; also, for the evidences 
they have given of interest in it. 
In reply to Dr. Campbell and Dr. Gregory, I wish to state that 
the ligature of to-day is not the ligature of twenty-five years ago. 
I put the greatest stress on the rendering of every kind of ligature 
aseptic; consequently we avoid the necessity of suppuration. It 
is possible and necessary in using animal ligatures to render them 117 
aseptic. I placed, also, stress on the behavior of ligatures, not 
capable of being absorbed, on the tunics of the vessels. I claimed 
for the animal ligature that it answers all the purposes of a tempo- 
rary ligature, that is, it answers the purpose of a haemostatic until 
closure of the vessel can take place; and to be that, a ligature 
which is found perfectly reliable and is substituted by healthy tissue 
possesses qualities which cannot be possessed by all. Catgut liga- 
ture is an effective ligature in every sense of the word. The other 
materials, more particularly that form which is not amenable to 
absorption, invariably produce division of the tunics of the vessel. 
They destroy the continuity of the vessel, and on that account are 
not desirable materials to be used in ligating arteries, more particu- 
larly near a large collateral branch. 
I placed stress, also, on the importance of ligating an artery near 
a collateral branch by making the space between the two ligatures 
bloodless, inasmuch as you afford more space for union; and I have 
no doubt that in the future we shall be able to ligate large arteries 
in the vicinity of large branches without the dangers of secondary 
hemorrhage. 
In regard to the remarks of Dr. Nancrede, of experiments on 
animals, I would say that experiments in the lower animals answer 
just the same results as in the human subject; consequently I 
believe that we are warranted in asserting that the experiments are 
simply a repetition of the phenomena which occur in the ligation of 
an artery in the human subject. 
I have also placed stress upon the importance of antiseptic pre- 
cautions in ligating any vessels, but more particularly in operating 
upon veins. Secondary hemorrhage is almost always the result of 
inflammatory changes at the seat of operation. Anything which 
will avoid an undue amount of inflammation or prevent suppuration 
will secure primary union of the wound and closure of the vessel.