[From the Dental Cosmos, March, 1869.] 
ACTION 
or 
ANESTHETICS ON THE BLOOD CORPUSCLES. 
BY J. H. McQUILLEN, M.D., D.D.S., 
PROFESSOR OF PHYSIOLOGY IX PIIILADELPHIA DENTAL «0^,EOE. 
In the October number of the Dental CosMO^a'report was presented 
of a series of experiments performed by me, on a number of animals, 
with the view of ascertaining whether the assertion made by a distin- 
guished experimentalist and scientist of England, that nitrous oxide, 
even under the most delicate manipulation, would prove destructive to 
life, could be possible. These experiments, which clearly demonstrated 
the assertion to be unfounded, were not performed in private, but in the 
presence of a number of gentlemen whose experience in the use of anes- 
thetics and whose scientific knowledge made them competent judges. 
First performed before the members of the Odontographic Society of 
Pennsylvania, they were repeated, after an interval of three weeks, on 
the same animals, in the presence of the members of the Biological and 
Microscopical Department of the Academy of Natural Sciences. 
A month subsequent to the last-named occasion, one of these animals, 
a rabbit, in the presence of a number of gentlemen, was placed under 
the influence of nitrous oxide, and kept in a profound state of narcosis 
for one hour and jive minutes, by alternating atmospheric air and nitrous 
oxide, removing the inhaler ever and anon for that purpose. Without 
question the animal could have been kept in the same condition double 
or treble the time without injury to it, for in a few minutes after re- 
moving the anaesthetic entirely, the animal was restored to conscious- 
ness, and leaped from the table to the floor, and for a number of weeks 
after this ran about my premises in a healthy and lively condition, and 
no doubt would have been still alive had I not demonstrated on him 
before the students of the Philadelphia Dental College the absorption 2 
of fats by the lacteals of the villi of the intestines, below the duct of 
the pancreas, and also the action of the heart and lungs; necessitating 
as this did opening into the abdomen and thorax, life of course became 
extinct. 
When under the prolonged influence of nitrous oxide referred to, one 
of the blood-vessels of this animal was opened for the purpose of exam- 
ining the blood corpuscles under the microscope, and ascertaining 
whether they had become disintegrated or any change had taken place 
in their form. On examination no perceptible difference was observable 
even after this lengthened exposure to the anaesthetic, when compared 
with the blood of another rabbit, which was not under its influence. 
This result induced me to examine into the statements made by Dr. 
Sansom, relative to the action of anaesthetics on the blood corpuscles 
in his highly interesting and able work on chloroform.* 
Prior to giving a description of my experiments in this direction, 
it may be proper to briefly refer to the prevalent theories on the phy- 
siological action of anaesthetics; also to the experiments performed and 
conclusions arrived at by Dr. Sansom. The view generally entertained 
is that first suggested by Flourens, that these agents act directly upon 
the nerve centres, producing regular and progressive modifications in 
the functions of the brain and spinal axis, first affecting the cerebral 
hemisphere, then the power of co-ordination in the cerebellum, then the 
conduction of sensation and motion in the spinal cord, and lastly, if the 
agent is pushed so far as to decidedly impress the medulla oblongata, 
suspension of respiration and circulation. 
Dr. John Snow, regarding this theory as an erroneous one, and re- 
cognizing ether, chloroform, and other anaesthetics as non-supporters of 
combustion, advanced the theory that these agents interfering with the in- 
troduction of oxygen into the system, induced their effect b}rthe suspen- 
sion of oxygenation, he therefore asserted that “narcotism is suspended 
oxygenation.” This view is embraced and strongly advocated by Dr B. 
Ward Richardson (the friend, biographer, and editor of his work on 
“Chloroform and other Anaesthetics”), and in England, apparently, is 
being very generally adopted by writers on this subject; Dr. Kidd, who 
has devoted much attention to the study of the action of chloroform, 
is, however, a prominent exception. 
Dr. Sansom, accepting this theory, and knowing that nitrous oxide is 
not only an anaesthetic but a supporter of combustion, recognized the 
necessity of presenting something more conclusive in the support of the 
view, than had heretofore been offered. He therefore in a paper read 
before the Royal Medical and Chirurgical Society, in 18(51, as the result 
* Chloroform, its Actions and Administrations. By Arthur Ernest Sansom, 
M.B., London: Lindsay & Blakiston, Philadelphia. a 
of certain experiments performed on the blood corpuscles of man and 
animals out of the body, attributed the influence exerted by anaesthetics 
on the nervous system to their acting directly upon the blood corpuscles, 
by modifying their form and integrity, and indirectly upon the nervous 
system through this altered condition of the blood, by interfering with 
its oxygenation. In his work he describes a series of six experiments; 
placing on glass slides, under a quarter-inch object-glass, human and 
frog’s blood, and subjecting them to the direct contact of alcohol, 
ether, and chloroform, which resulted quickly in the disintegration of the 
blood corpuscles, leaving nothing but their nuclei and debris of the 
walls of the corpuscles. From these experiments on blood out of 
the body, he states in the work referred to : “ The effect therefore 
of these agents upon the blood is solution — destruction. At first 
there is a change induced in the cell itself and upon the nucleus (in the 
case of frog’s blood). The globuline of the blood is acted upon as it 
were by a caustic. Finally the old corpuscle is destroyed and its color- 
ing matter set free.” * * * From the foregoing facts and other con- 
siderations, the author considers that certain conclusions in regard to 
the action of anaesthetics are warrantable. Anaesthetics are agents 
which when absorbed into the circulation exert an influence upon the 
blood. They are shown to have the power of altering its physical char- 
acter and physical properties. By an action upon its constituent (pro- 
teinous) elements, they tend to alter and by a profounder action to de- 
stroy its organic molecules. Its physical perfection being interfered 
with, its function is held in abeyance ; the changes which contribute to 
constitute perfect life are retarded. Narcosis ensues; and is due, not 
to the influence of a circulating poison, but to the influence of an altered 
blood. Further on he adds: “Narcotism (or to speak more particu- 
larly, chloroform narcotism) is due not to a special poison that ‘mounts 
up to the brain,’ but to an altered blood. Then ‘ narcotism is a suspended 
oxygenation ’ Whatever produces to a certain extent insufficient aeration 
of the blood, produces narcosis; and whatever produces narcosis, pro- 
duces by some means or other imperfect aeration of the blood.” 
In drawing these conclusions, of an altered condition of the blood, from 
appearances presented by the blood out of the body, Dr. Sansom evidently 
leaves it to be inferred that somewhat if not exactly analogous results 
are produced on the corpuscles in the body, when human beings or ani- 
mals are under the influence of anaesthetics by inhalation. After a 
patient, oft-repeated series of experiments performed by me during 
the past three months, not only on blood out of the body, but also in 
cases in which human beings and animals have been placed under the 
influence of ether, chloroform, and nitrous oxide, and the blood drawn 
from them prior to and after the administration of these agents has 
been carefully exavxined and compared, the results obtained compel me 4 
to take very decided exceptions to such conclusions being- justifiable in 
the premises. 
First Series.—The experiments were 
as follows: In my examinations of the 
blood of man and animals, when ether and 
chloroform were brought in direct contact 
with it out of the body, under a fifth ob- 
jective, the discharge of the nuclei and the 
disintegration of the corpuscles have in- 
variably occurred, and in the frog leaving 
a result similar to that which is presented 
in the accompanying drawing (Fig. 1), 
from one of my specimens, wherein it 
will be observed that the field is occu- 
pied by the nuclei, debris of disintegrated 
globuline and corpuscles, in which the 
change of form, size, and other characteristics are most striking. 
Second Series.—On placing, however, two glass slides containing 
frog’s blood over watch-crystals, one holding chloroform and the other 
ether, and covering them with glass finger-bowls for half an hour, thus 
exposing one to an atmosphere of ether, and the other of chloroform, I 
found, on removing the bowls, and permitting the bloody sides of the 
slides to remain downward, until all the ether and chloroform had evap- 
orated, that no disintegration or marked change in the form of the cor- 
puscles was observable under the microscope, on comparing them with 
the blood of a frog unaffected by an anaesthetic. This forcibly demon- 
strates the difference between exposure to direct contact and the vapor 
of chloroform, even out of the body. 
Third Series.—Over and again in the presence of a number of gentle- 
men, I have placed frogs under the 
influence of ether, chloroform, and 
nitrous oxide, and examined their 
blood corpuscles immediately after 
without finding any disintegration or 
change in the form of the corpuscle. 
In oiie instance, a frog was so com- 
pletely narcotized by chloroform that 
it died; the thorax of the animal was 
opened, the lungs cut out, and the 
blood obtained directly from that or- 
gan, and even here, where, if the 
inference of an altered blood was 
correct, there should have been dis- 
charge of nuclei, disintegration, or marked change in the form of the 
Fig. 1. 
Frog’s blood placed upon the slide, 
and chloroform brought in direct 
contact with it. 
Fig. 2. 
Corpuscles from the lungs of a frog which 
died under the influence of chloroform, 5 
corpuscle, nothing of the kind was evident, as will be seen by the ac- 
companying illustration, drawn from the slide on which the blood was 
placed. (Fig. 2.) . As already intimated, the experiments in this direc- 
tion have been prosecuted on every available occasion within the past 
few months; and I have not confined myself to frogs, but, in the course 
of vivisections on a large number of animals (rabbits, dogs, cats, and 
pigeons), to illustrate my course of lectures on physiology this winter, 
when these animals have been placed under the influence of ether or 
chloroform, their blood has been examined and no change in the form of 
the corpuscle has been evident. 
Fourth Series.—The examination of the blood of a number of human 
beings, drawn prior to and after hav- 
ing been under the influence of ether, 
chloroform, or nitrous oxide, for the 
extraction of teeth, has yielded simi- 
lar results, as will be evident from the 
accompanying illustration of the blood, 
obtained from a patient (Fig. 3), while 
under the influence of chloroform. 
Any one accustomed to microscopical 
examinations will recognize the nor- 
mal characters of the corpuscles, so 
far as it is possible to present them in 
a wood-cut. 
The results of these investigations were recently presented to the 
members of the Microscopical and Biological Department of the Acad- 
emy of Natural Sciences, illustrated by a large number of microscopical 
slides, and although some time has elapsed since the blood was placed 
on many of them, the corpuscles retain their form unchanged. 
Presenting the statements for what they are worth, and desiring that 
others may either confirm or disprove them by experiments of their 
own, as carefully conducted and as frecpiently repeated, and not merely 
performing a few experiments and then drawing conclusions which 
they would not be warranted in doing, I would suggest to such that 
there are two modes of preparing blood for microscopical examina- 
tion, each of which has been tried in my investigations. First 
plan—the blood, placed on a slide, is spread with a knife-blade 
thinly over the glass, then waving it backward and forward in 
the air, the blood is dried by evaporation, and can be covered with 
a thin glass slide, cemented, and kept for a considerable length of 
time without change. Second plan—a drop of blood is placed on the 
slide, a thin glass cover is brought in contact with the edge of the 
drop, and by capillary attraction, a stratum of blood is drawn under it. 
Although this answers for immediate examination, unless some men- 
•Fig. 8. 
Corpuscles of a patient under the influ- 
ence of chloroform. 6 
struum is employed for the preservation of the blood, its characteristics 
become so completely changed in the process of coagulation that the 
specimens become useless. In pursuing these investigations, care must 
be exercised to prevent the direct contact of ether and chloroform with 
the blood corpuscles, as this makes the greatest possible difference. 
In conclusion, although it is not my intention in this communica- 
tion to engage in an extended inquiry relative to how anaesthetics 
produce their effects, it seems to me that the above experiments demon- 
strate that we are not warranted in denying that these agents act 
directly upon the nerve centres. All the phenomena, indeed, attendant 
upon their administration, the gradual exaltation of the cerebral 
functions followed by the progressive impairment and temporary sus- 
pension of the special senses, the loss of co-ordination on the part 
of the cerebellum, and when the agent is pushed too far, the arrest of 
respiration and circulation through the decided impression made upon 
the medulla oblongata, seem to favor this hypothesis, in contradistinc- 
tion to the theory that anaesthesia is due to suspension of oxygenation. 
In connection with this, I cannot refrain from saying, when taking 
into consideration the readiness with which fluids absorb gases, that 
undue prominence apparently has been given by physiologists to the 
blood corpuscles as the carriers of oxygen to the tissues, and carbonic acid 
gas to the lungs, for it is reasonable to infer that the liquor sanguinis 
is actively engaged in this operation. After the most careful examina- 
tion under the microscope, I have been unable to observe those modifi- 
cations in the form of the corpuscles in venous and arterial blood, chang- 
ing from biconvex to biconcave disks, and attributed to the absorp- 
tion of the gases, of which so much is said in the books. That anaes- 
thetics, when acting directly upon the nerve centres, may interfere with 
the oxygenation of the nervous mass, is possible, but it is to be viewed 
rather as an effect than as a cause of narcosis. Again, even admitting 
that such agents as chloroform and ether, by interfering with natural 
respiration and the ox}rgenation of the nervous mass, might possibly 
produce their result in that way, it is difficult to understand how this can 
be brought to bear upon an agent like nitrous oxide, which contains an ex- 
cess of oxygen over atmospheric air. To those who may assert that 
nitrous oxide is a compound (and not a mixture like atmospheric air), 
and therefore incapable of decomposition and furnishing oxygen to the 
nervous mass, I would remind them of a law in chemistry, that when 
two compounds, the elements of which have a stronger affinity for each 
other than the compounds in which they exist, are brought in contact 
under favorable circumstances, a mutual decomposition occurs, and new 
compounds are formed in their place. It may be said that the condi- 
tions in the body are not favorable to such results; but who shall have 
the temerity to assert that, when recalling the incessant compositions and 7 
decompositions of a chemical character taking place in the body, fully 
recognized and admitted by those who insist most upon the controlling 
influence of vitality? It is a well-known fact, that nitrous oxide is a sup- 
porter of combustion, and that a lighted candle burns with increased bril- 
liancy in it; here the combination of the nitrogen and oxygen in definite 
proportion is not so strong but that the carbon of the candle is able to 
seize upon the oxygen, and augment the size of the flame. The function 
of respiration consists in a mere interchange of gases, of the exhalation 
of carbonic acid gas and the introduction of oxygen; the latter, absorbed 
by the blood, is carried to the nervous mass and other tissues, and results 
in their oxygenation, a slow form of combustion, which is but a difference 
in degree with the burning of the candle. If, then, the nitrous oxide, as 
can be readily demonstrated, yields up its oxygen to support the burn- 
ing of a candle, where is the philosophy in denying that it may also as 
freely give up its oxygen to a tissue which has such a strong affinity for 
it as the nervous mass, when they are brought in direct contact with 
each other ? 
In addition to these arguments, it should be remembered by the 
readers of this magazine, that in cases of impending asphyxia from 
drowning, hanging, inhalation of noxious vapors, etc., of a 
number of animals experimented upon by my friend and co-laborer, Dr. 
Geo. J Ziegler, animation was promptly restored in every case by the 
injection of nitrous oxide water into the intestines of the animals. In 
these cases the efficacy of this agent in supplying oxygen to the blood 
and the nervous mass was most satisfactorily demonstrated. 
If we assume that the influence of anaesthetics is dependent not upon 
a direct action on the nerve centres,-but to an altered condition of the 
blood and the suspension of oxygenation, we must apply the same prin- 
ciple to all diffusible stimulants. 
In a forthcoming number of the magazine, I shall present a series of 
experiments of the results obtained from the direct contact of anaes- 
thetics with the different portions of the nervous system.