Is the Cause of Respiration the 
Venosity of the Blood and 
Tissue Fluid in the Re- 
spiratory Center of the 
Medulla Oblongata? 
BY 
W. Y. COWL, M. D. 
BEPBINTED FROM 
Neto York f¥letoc*l journal 
for June 6, 1891. Reprinted from the Rew York Medical Journal 
for June 6, 1891. 
IS THE CAUSE OF RESPIRATION 
THE VENOSITY OF THE BLOOD AND TISSUE FLUID IN 
THE RESPIRATORY CENTER OF THE MEDULLA OBLONGATA? 
By W. Y. COWLED. 
In the issue of this Journal for November 22d last, in 
an article entitled Some Remarks on my Hypothesis of the 
Self regulation of the Respiration and Dr. Cowl's Discus- 
sion of it, Dr. S. J. Meltzer asks my attention to the subject 
of the causation of respiration in the question hereafter 
following. 
To this, by reason of the directness of the query, I de- 
sire briefly to respond, while at the same time expressing 
my satisfaction that he has not felt called upon to contro- 
vert the cogency of the facts I have adduced * to show the 
irrelevancy of the experimental results brought forwaid by 
him as a basis for his theory of the incitation of inspira- 
tion, f as well as the groundlessness of his criticism upon 
* The Factors of the Respiratory Rhythm and the Regulation of 
Respiration. TV. Tr. Med. Jour., Sept. 6, 1890. 
f On the Self-regulation of Respiration. Ibid., Jan. 18, 1890. 
Copyright, 1891, by D. Appleton and Company. 2 
THE CAUSE OF RESPIRATION. 
the existing theory of respiratory regulation, formulated 
and established by Gad.* 
He asks, in general terms: " Does Dr. Cowl know of 
any experiment which shows that the blood, and that alone, 
is the exciting cause of respiration?" 
For putting this question the author gives no grounds 
beyond a mere reference to my citation of a number of 
observers, who have shown the high sensitiveness of the 
respiratory center to changes in the constituents of the 
blood, and does not advert to those portions of my com- 
munication respecting the causation of respiration, or allude, 
except in two instances, to the published labors of the chief 
workers on this subject. 
As, furthermore, he does not specify, on the one hand, 
whether he means simply the ordinary continuous respira- 
tion or also extraordinary respiratory efforts thereupon im- 
posed, and, on the other hand, excludes from consideration 
the tissue fluids, which, from their constant renewal by the 
blood as well as because of the free diffusion of the gases 
dissolved therein to and from the vessels, are equally to 
be regarded (11), 1 can not assume to understand his 
meaning. 
But, although this vagueness of his interrogation would 
call for explanation, I shall, rather than give rise to further 
disquisition, simply amplify in the required direction the 
basis of fact that I have previously given, and show the 
support which those facts are widely conceded to furnish 
for the essential causation of respiration by the excitants of 
the blood, by those substances, namely, which when in- 
creased in amount occasion increased respiration. This is 
of itself, at the present time, no ungrateful task, as the 
knowledge of the subject already established has, within 
* Die Regulirung der normalen Athmung. Du Bois-Reymond's 
Archiv, 1880, p. 1. THE CAUSE OF RESPIRATION. 
3 
the past few years, received a decided enrichment, which 
is not yet become common property. 
In view of this enrichment, it may be said in advance, 
in respect of the known facts concerning the innervation 
of respiration altogether, that they solve, on the one hand, 
the problem of how it is that the first inspiration at birth 
comes to take place, and furnish, on the other, positive 
knowledge of the only means as yet demonstrated for the 
continuous incitation of respiration. By them, further- 
more, the idea enunciated by Marshall Hall (1) that res- 
piration was a reflex act wherein the incitation flowed to 
the respiratory center * from the brain, from the vagus, or 
from the sensory nerves in general, an idea which, notwith- 
standing a mass of experimentation directed toward its 
proof in these several respects, has at no time been shown 
to account in either of these ways for more than extraor- 
dinary respiratory efforts-e. g., sighing, coughing, sneez- 
ing, anxious breathing-is now very definitely settled in 
the negative. 
The theory of the peripheral origin of the incitation to 
respiration in general, of which Dr. Meltzer, in his former 
article, is the last exponent, would, by reason of its lack of 
support, have probably long since become disregarded were 
it not that it was broached in the first pretentious work 
upon this subject, and that it is a matter which is so appar- 
ent to the eye that the common extraordinary respiratory 
efforts result reflexly from sensorial impressions. 
The first of the researches, which go to show that the 
incitation of inspiration is central and direct, and not pe- 
ripheral and reflex, is that of Schwartz (2), entitled Prema- 
ture Respiratory Efforts ; a Contribution to the Effect of 
* The commonly so denominated mechanism for the innervation of 
the respiratory efforts located in the medulla oblongata, and in general 
indispensable to respiration. THE CAUSE OF RESPIRATION. 
4 
the Act of Birth upon the Foetus, published in 1858, and 
noticed by Miescher (3) in the general article on the inner- 
vation of respiration contained in Du Bois-Reymond's 
Archiv for 1885 and cited in my previous communication. 
It is there stated that, " as the hinge upon which the exist- 
ing view respecting the cause of the respiratory motions 
depends, the continually recurring question has been re- 
garded, how, over against the quietude of uterine existence, 
does the first breath drawn come to take place ? Is it the 
sensorial excitations of the act of birth, the cooling, the 
mechanical measures, by the fit application of which the 
halting respiration of the half-asphyxiated child is so be- 
neficently aided, or does there lie something at bottom 
in the blood of the foetus which is changed by the act of 
birth ? 
" It is the same contradistinction which from the be- 
ginning until to-day permeates all discussions upon the 
respiratory movements, and, although the controversies are 
to-day more complicated than before, they are so, however, 
because various changes in the blood and various sensorial 
influences strive, as it were, for the governing place, or at 
least for a part of the territory. 
" In view of so many apt statements of the older theo- 
ries of respiration as exist, it will suffice for our object if 
we devote our discussion to the turning-point which the 
question of the origin of the first respiration passed by 
in the renowned work of Schwartz in 1858. 
" Since Schwartz developed, more logically than had 
before been done, the idea that the premature respiratory 
movements of the foetus, so feared in difficult labors, were 
always to be referred to some disturbance of the placental 
circulation-to cessation, therefore, of gaseous interchange 
between mother and child-this same mode of view has de- 
termined the conception of ordinary respiration, and this THE CAUSE OF RESPIRATION. 
5 
has been clearly formulated and established in part through 
new researches by Rosenthal." 
A second well-recognized work, by B. S. Schultze (4), 
which supports Schwartz's position, entitled Apparent Life- 
lessness in the New-born, is, like that of Schwartz, unfortu- 
nately, not at my command. 
Within the past few years, however, two more complete 
experimental confirmations of the same idea have appeared. 
First, Zuntzand Cohnstein (5), in Some Further Researches 
on the Physiology of the Mammalian Foetus, in treating of 
the causes of the normal apnoea* of the foetus and of the 
first respiratory efforts of the new-born, record the following 
experiment upon the sheep, in which animal the placental 
tufts are so distributed about the walls of an unusually lax 
uterus that the opening of the latter and the extraction of 
the foetus cause no interference necessarily with the pla- 
cental circulation : 
The research in question was made on February 2, 1885. 
At first only the tail and a fraction of the fore part of the trunk 
were exposed to the air. 
Pinching, pricking, excitation of the pharynx and of the 
mucous membrane of the nose incited no inspiration. 
Upon this, the animal was entirely extracted from the uterus 
and laid upon the abdomen of the mother, with careful avoid- 
ance of all traction upon the cord. Excitations now continued 
for several minutes, to which we added injection of air into the 
nose with a bellows, also produced no respiratory movement. 
The excitations mentioned induced numerous motor reflexes. 
The new-born animal sucked the finger and bit it when intro- 
duced deeper into the throat. Reflex motions did not regularly 
follow the excitations, but, on the other hand, there appeared 
frequent strong, spontaneous movements, which occasioned 
changes of position of the foetus. The mucous membranes 
showed a normal red hue; no trace of cyanosis. 
* Temporary absence of intermittent respiratory effort. 6 
THE CAUSE OF RESPIRATION. 
The first breath drawn followed almost immediately upon a 
ligation of the umbilical cord, and was succeeded by regular 
respiratory movements without any rattling. The foetus con- 
tinued to live. That it was full grown is proved by the weight 
of 2,860 grammes, the length of 48 centimetres, the develop- 
ment of the wool, and the energetic ingestion of nourishment. 
It took at the first drink, about an hour after the tying of 
the cord, 60 grammes of milk. 
We had therefore a normally apnoeic foetus under our hands, 
which was brought to breathe by no kind of excitation, but at 
once by cutting off the supply of oxygenated blood through the 
umbilical cord. 
The authors note, in connection with this experiment, a 
source of deception which, in common with B. S. Schultze, 
they find in the usual means of inferring an absence of in- 
crease in the venosity of the blood actually furnished to the 
tissues of the foetus (i. e., mixed blood already considerably 
venous)-namely, by the brightness of color of the umbili- 
cal vein-for, as they very fully show, whenever the foetal 
circulation is slowed, whether in the foetus itself, as by an 
infrequency of the heart's action, or by compression of the 
umbilical vessels, the blood remains a longer time in the 
tufts of the placenta than otherwise, and therefore becomes 
more completely arterialized and of a brighter hue. 
Thus, just when the blood in the umbilical vein, from 
its longer sojourn in the placenta, is more highly arterial- 
ized than normally, the tissues of the foetus-its respiratory 
center therefore-are, nevertheless, suffering from a lack of 
arterial blood, a lack which affects both the quantity and 
quality of its supply ; dyspnoea will, therefore, necessarily 
be developed, the same as by a slowing of the cerebral cir- 
culation in the grown animal (6). 
O. Engstrom (7) has carried out in Preyer's laboratory 
a similar series of researches upon rabbits and guinea-pigs 
and in part by opening the uterus under warm salt water. THE CAUSE OF RESPIRATION. 
7 
He finds, like the above-mentioned authors, that mechani- 
cal irritation of the foetus alone will not induce respiration, 
but that stoppage or diminution of the placental circulation 
without such irritation will do so. He ascribes, neverthe- 
less, to sensorial impressions a part in the excitation of the 
first breath drawn by the foetus in general. 
From the evidence, then, altogether, respecting the inci- 
tation of respiration at birth, we are justified in the state- 
ment that the essential cause of the first respiratory effort 
is the increased venosity of the blood supplied to the respi- 
ratory center of the foetus. 
That at many human births the foetus does not respire 
until marked sensorial impressions be made upon it might, 
in view of the practice of delating the ligation of the cord 
until respiration is established, be ascribed to a greater or 
lesser continuance of the placental respiration. How con- 
siderable, at any moment after normal birth, this latter res- 
piration in general may be, we have as yet no accredited 
data for determining. Doubtless, whenever the uterus, 
freed from the bulk of the foetus and the resistance to its 
birth, continues in contraction, the placental respiration 
must have ceased or have become much diminished, where- 
upon, by the direct resulting effect upon the respiratory 
center, and possibly also by the sense of cold to the sur- 
face, a respiratory effort, if nothing be there to hinder, will 
at once be induced. When, on the other hand, there are, 
after birth, intervals of non-contraction of the uterus, pla- 
cental respiration may still continue and be sufficient for 
the needs of the foetus. 
The escape of blood of a markedly venous hue from 
the placental stump of the umbilical cord upon cutting it, 
after aerial respiration has begun, has evidently no certain 
bearing upon the question of persistence of placental circu- 
lation before this time, and may therefore be disregarded. 8 
THE CAUSE OF RESPIRATION. 
Those infrequent cases in which the cord is cut before 
respiration is established, chiefly in order to more effective- 
ly carry out measures of artificial respiration, are certainly 
in general, if not always, abnormal. A cause of halting res- 
piration is obviously present, which is greater in its hinder- 
ing effect than the increased venosity of the blood from the 
cessation of the placental functions, together with the pe- 
ripheral excitations incident to birth, are in their incitatory 
action. This cause-the respiratory passages and other 
parts being normal-must be an abnormally diminished 
excitability of the respiratory center, and this may be 
explained by a previous prolonged diminution or cessa- 
tion of the oxygen supply upon which the excitability 
of the center depends. A slight diminution in that sup- 
ply in the foetus must prevent respiration by allowing 
the excitability to sink below the point of effective excita- 
tion by the excitants offered to it by the blood and tissue 
fluid. 
Thqt the center normally possesses a markedly lesser 
degree of excitability in the foetus than in the breathing 
animal has been rendered in the highest degree probable 
by Zuntz and Cohnstein (5); for, upon adding one per 
cent, of carbonic acid, as an excitant of increased respira- 
tion, to the respired air, at intervals for several days after 
birth, they found a continuous increase in the excitability 
of the center-an increase which they attribute to develop- 
ment of the same. As effective causes of such development 
of the center, there are the beginning of its function and 
the marked increase in the arterialization of the blood fur- 
nished to it upon the separation of the systemic and pul- 
monary circulations at birth; moreover, the blood of the 
umbilical vein itself can not necessarily be so well arterial- 
ized as the blood in the arteries of the self-respiring ani- 
mal, which is shown, under normal circumstances, by the THE CAUSE OF RESPIRATION. 
9 
fact that, as previously stated, the vein grows of a brighter 
red when compressed. 
But this increased arterialization after aerial respiration 
is established coincides with increasing tissue activity gener- 
ally; for Zuntz and Cohnstein (5) find that the differences 
between the respective amounts of carbonic acid on the one 
hand and of oxygen on the other in the blood of the um- 
bilical vein and artery are, in each case, but about one half 
the difference between the same in the carotid artery and 
jugular vein, respectively, of the breathing animal. In es- 
timating, furthermore, the actual consumption of oxygerf 
by the tissues of the foetus, a determination of the normal 
amounts of blood delivered to them in a unit of time ena- 
bled these observers to make a comparison between the 
foetus and the grown animal, whereby it was found that the 
latter consumed about four times as much oxygen as the 
former. These observations showing a lesser consumption 
of blood in general before birth explain the low excitability 
of the foetal respiratory center. 
A diminution of the excitability of the respiratory center 
has been shown by Gad (6) to result, in the grown animal, 
from a diminished supply of arterial blood to that center. 
Similarly, upon the normally lower excitability of the re- 
spiratory center existing in the foetus, a diminution may, 
furthermore, be imposed by conditions surrounding it for 
a time before birth attending the contraction of the uterus. 
This contraction acts, first, by lessening the placental 
respiration through hindrance of the maternal placental cir- 
culation and through slowing of the circulation in the foetus 
by slowing of its heart's action ; secondly, in cases of head 
presentation, by directly diminishing the intracranial cir- 
culation. When the uterine contraction is quite persist- 
ent, as often occurs in these latter cases, the consequent 
diminution of excitability in the respiratory center may be 10 
THE CAUSE OF RESPIRATION. 
greater than the increase in the normal excitants of the 
blood resulting from the diminution of the placental respi- 
ration can compensate for; for, while the cranial pressure 
directly occasions an additional diminution of the excita- 
bility of the center, it does not, like the interference with 
the placental respiration, occasion corresponding increase 
of the respiratory excitants in the foetal blood at large, but 
rather, indeed, by inhibiting muscular action, diminishes 
their production. Its direct influence remains, moreover, 
a superposed one when we take into account the fact that 
such pressure alone as found by Zuntz and Cohnstein will 
effect a slowing of the pulse and a slowing of the foetal cir- 
culation, as evidenced by an increased brightness of color 
of the umbilical vein. 
It is altogether, then, easy to perceive how, notwith- 
standing a ligation or section of the umbilical curd, a foetus 
may not breathe. The greater frequency, moreover, of 
such a condition of non-respiration in a viable foetus in 
man than in the lower animals coincides with the relativelv 
larger size of the head in him. He has special need, there- 
fore, of the accessory provisions for the incitation of the 
first inspiration furnished by nature, such as the response 
to the impression of cold or of flagellation. The action of 
these latter may evidently be either by reflex incitation of 
the center, or by increasing, more or less indirectly, through 
the general excitement, the excitability of the respiratory 
center to the normal direct excitants; in the former case 
they are immediately causative, in the latter evidently only 
conditional of respiration. 
Cognizant of the extraordinary conditions at birth, that 
by exaggeration call at times for the marked action of the 
accessory provisions for the incitation of respiration in 
order to occasion the first inspiration ; but, in view of the 
decisive fact that the hajmic excitants of respiration are THE CAUSE OF RESPIRATION. 
11 
normally of themselves sufficient to occasion that effort, 
and that, despite the pulmonary arterialization of the blood, 
venous elements to a considerable amount still remain 
within it, we have the strongest possible presumption that 
the succeeding respirations-namely, the regular respira- 
tory muscular action-are likewise incited through the 
venosity of the blood and tissue fluid contained within the 
respiratory center. 
The further support for this position is contained in 
the proof -of the great sensitiveness of the respiratory 
center in the more developed animal to changes in the con- 
stituents of the blood, and in a certain definite provision 
which has been shown to exist for the incitation of in- 
creased respiration, and to be directly due to increased tis- 
sue change within the organism (11). 
Since the experiments of Traube, who held that the 
vagus was excited by the carbonic acid of the venous blood 
in the lungs (10), it has been known that the respiration 
of air containing this gas would evoke dyspnoea, and it has 
been shown in man by Miescher (3) that an addition of but 
one per cent, of this gas to the air respired results in a de- 
cided increase in the amount of air breathed, even without 
the knowledge of the subject of experiment. Traube's 
idea has gradually been given up, and it is now found by 
A. Loewy (8) that the sane amount of increase in respira- 
tion on breathing air vitiated with carbonic acid occurs 
when in the animal the vagi are divided as when they are 
intact. From this it is most probable that such an increase 
of respiratory effort in man is not owing to excitation of 
the vagus by the venous blood or its carbonic acid in the 
lungs. 
Very recent researches by Gad (9) concerning the deep 
inspirations which have been immediately induced by an 
inhalation of pure carbonic acid, or a strong admixture 12 
THE CAUSE OF RESPIRATION. 
thereof with air, show that this excitative action of carbonic 
acid is confined to the trachea and chief bronchi-parts not 
in contact with the venous blood laden with carbonic acid; 
and also that an atmosphere containing at least fifty per 
cent, of the gas is necessary to produce the reflex, a pro- 
portion greater than occurs even in the exhaled air from an 
almost asphyxiated animal. It is therefore clear that this 
excitant of respiration does not normally act by means of 
the vagus nerve. That, on the other hand, it does not first 
act upon the brain, and from thence reflexly upon the res- 
piratory center of the medulla oblongata, but directly upon 
the latter, is rendered most probable by the observation of 
A. Loewy (8), that a like amount of increase of respiration 
upon adding a certain amount of carbonic acid to the re- 
spired air occurs before and after separating these nervous 
masses. 
Thus Marshall Hall's first two alternatives are excluded; 
the third, that sensorial impressions occasion respiration, 
which was developed by Volkmann into the theory that 
the incitation to respiration lies simply in the excitation by 
carbonic acid of the sensory nerves in general, may be con- 
sidered to be excluded, first, for respiration as a whole, by 
the experiment of Rosenthal (13), in which rhythmic respi- 
ration continued after all but a few of the sensory paths to 
the medulla oblongata were divided, an experiment that 
has since been repeated with greater completeness and the 
same result; and, secondly, for the proportionment of the 
amount of respiration to the needs of the organism, through 
the researches of Zuntz and Geppert (11). The latter 
found, by measuring the air respired, together with the 
amounts of oxygen consumed and of carbonic acid given off, 
by an animal under three different conditions-namely, of 
rest, of accustomed labor, and of muscular activity induced 
after section of the spinal cord above the origin of the THE CAUSE OF RESPIRATION. 
13 
sciatic nerves by electrical excitation of these in their course 
-that, with the same increase of the respiratory inter- 
change of oxygen and carbonic acid, denoting the same 
degree of muscular activity in the third as in the second 
case, the amounts of air respired were also the same, or 
nearly the same, in these latter cases. 
Furthermore, upon cutting off the circulation in the act- 
ive parts during the muscular excitation in the third case, 
the increase in respiration over that at rest failed to appear, 
and only did so when the vessels were let free, whereby 
the carbonic acid and other substances formed in the mus- 
cles during their activity came into the general circulation 
and thus reached the medulla oblongata. 
Similar results have been obtained also by A. Loewy 
(8) in researches in which the brain was separated from 
the medulla oblongata, the spinal cord bisected in the mid- 
dorsal region, and the vagi divided. 
It is evident from the foregoing, altogether, that the 
increased respiration during muscular activity was due to 
the venosity of the blood circulating in the respiratory 
center, and not to that in the tissues in general, nor to any 
sensorial impressions. 
It is, moreover, plain from these experiments that a 
provision exists in the substances formed by muscular ac- 
tivity by which the amount of respiratory effort is directly 
governed at the respiratory center. That such a propor- 
tionment of the amount of air breathed to the need for it is 
in play, not only during pronounced muscular exertion, but 
also in that condition we denominate rest-a condition in 
which, when the skeletal muscular system is relatively quite 
relaxed, the main activities of the organism are the muscu- 
lar contractions concerned in circulation, respiration, and 
the general production of heat (Fick, Pfliiger)-is highly 
probable; is, indeed, tacitly assumed by Zuntz and Geppert. 14 
THE CAUSE OF RESPIRATION. 
But, if this is so, it affords a further support of the accepted 
view that the venosity of the blood and tissue fluid in con- 
tact or proximity with the substance of the respiratory cen- 
ter regulates the amount of respiration, which must then, in 
the existing absence of proof of other means of constant in- 
citation of respiration, be considered to afford that continu- 
ous incitation altogether. We therefore consider it so, and 
might indeed refuse to entertain speculation as to whether 
sensorial impressions may in any way be concerned in this 
regulation, but a possibility seems nevertheless to exist that 
ordinary respiration is somewhat greater in amount than it 
otherwise would be by reason of a constant effect upon the 
respiratory center produced by sensorial impressions height- 
ening its excitability to the normal direct excitants. This 
is, a priori, improbable, as the amount of respiration would 
then depend, not upon the needs of the organism as deter- 
mined by tissue change, but upon the amount of nervous 
action present, which might or might not coincide there- 
with ; again, supposing that efficient respiratory action was 
insufficient by reason of a failure of its help, it would add 
at least unnecessarily to the mechanism. But, beyond this, 
there is direct evidence to the contrary, namely, the obser- 
vation by Loewy (12), that sleep both natural and arti- 
ficially induced-e. g., by chloral hydrate-does not alter the 
excitability of the respiratory center, while greatly re- 
ducing the amount of respiration through diminished 
formation of the normal direct excitants in the tissues in 
general. 
That, in general, under extraordinary circumstances, 
the respiration may be increased by sensorial impressions 
needs no exemplification ; but a continuance of such in- 
crease after the first breath or two is to be attributed to 
increased muscular or other activity induced by the same 
nervous impressions. THE CAUSE OF RESPIRATION. 
15 
We are altogether, therefore, restricted to the venosity 
of the blood as the essential cause of the ordinary normal 
continuous respiration. 
The one factor of this venosity which is positively known 
to be an excitant of the respiratory center is, as previously 
stated, carbonic acid. Of the others, a diminished alkales- 
cence of the blood, occasioned by the formation of a more 
active acid than carbonic (lactic) in the muscles during their 
activity, is known (14) to diminish the receptivity of the 
blood for carbonic acid, thus effecting an increase of the 
latter in the tissues. 
Lack of oxygen in the blood furnished to the medulla 
oblongata is in all probability never so great under normal 
circumstances as to give rise to excitation of the respira- 
tory center; for a reduction in the amount of oxygen in a 
respired atmosphere to below 17 per cent, must take place 
before dyspnoea is developed, and before this point is 
reached there is already a reduction in the amount of oxy- 
gen consumed by the organism, as shown, respectively, in 
researches by Gad (15) and by Kempner (16). 
In contradiction of the prevailing view of the central 
incitation of respiration, the only published researches are 
those of Marckwald (17), which are cited by Meltzer, to- 
gether with an old experiment of Volkmann's, undertaken 
for another purpose, but lending itself to the arguments and 
cited by the first-named authors. 
Marckwald's position is thus comparatively isolated. It 
has already received a very full reply, with experimental 
proof, to which I would refer (8). His main conclusion, 
thereby controverted, differs diametrically from those of 
Rosenthal, Pfliiger, Gad, Zuntz, and numerous others in 
their researches. It is as follows : "The normal excitation 
of the respiratory center is not dependent on incitation 
upon the part of the blood, neither from deficiency of oxy- 16 
THE CAUSE OF RESPIRATION. 
gen nor from excess of carbonic acid in the blood," and is 
immediately followed by its support, to the effect that 
''animals without circulation and after exsanguification may 
continue to breathe for a long time." 
Respecting this position and its supportive facts I 
would only note in particular that Marckwald and also Melt- 
zer seem not to perceive that excitants ot the respiratory 
center are necessarily still present in its tissue, being, un- 
der normal circumstances, only governed as to the amount 
there held by the amount of the same substances, or of 
other substances influencing their solubility, in the blood 
delivered to that center. Be there at any moment suppos- 
edly no carbonic acid within the tissue of the center, it 
must immediately diffuse thereto from the blood in the sur- 
rounding vessels. Be the blood, on the other hand, more 
or less drained from those vessels, as in the experiments of 
Volkmann and of Marckwald, or completely removed, as in 
some of the latter's researches, carbonic acid, nevertheless 
still remains in the center, and will continue to be produced 
there as long as substances are contained within the same, 
available to the generation of thife product of tissue activi- 
ty, and for just so long, probably, will the center con- 
tinue to perform its function of inciting respiratory effort. 
In illustration and support of this explanation of the con- 
tinuance of respiration in Marckwald's experiments, I would 
call especial attention to the latter portion of a remark con- 
cerning them that accompanies the description of one of 
the same, in which, after a removal of the blood in the 
vessels of the respiratory center by means of an injection 
of paraffin, the respiration still for a time continued. The 
observation is as follows : " 1 had frequent opportunity in 
animals bled to death (in the dog as well as the rabbit) to 
note the same [«. e., respiratory effort], and chiefly when 
they had been bound for a long time." Now, it is ap- THE CAUSE OF RESPIRATION. 
17 
parent from this that the respiratory function was at a 
minimum of activity, in which case, as is evident from 
our knowledge of the longer retention of functional power 
in the relatively less active respiratory center of the new- 
born than in that of the grown subject when deprived of 
air, the center would not so quickly lose its excitability 
on cutting off the blood supply as in the fresh animal, 
whereas the formation of carbonic acid there would be a 
diminished one, and therefore less quickly exhaust the cen- 
ter through the excitation offered by its progressively in- 
creasing amount. 
Hence, so long as the center preserves a sufficient ex- 
citability after the cessation of the supply of fresh blood, 
so long will it continue to act. If the center has been 
ordinarily active, the stoppage of the blood-supply will be 
of quicker effect than when the animal be lethargic, hyp- 
notized, or narcotized. 
The same argument applies to Volkmann's experiment 
(18), which is of a similar character to those of Marckwald. 
The former is, however, interesting to us here, because of 
the object its author had in making it-namely, to show 
that respiration is not incited by means of the vagus or of 
the brain, as well as because of the particular fact devel- 
oped and others contained in the description, which reads 
as follows: "I removed in a young cat the brain, with ex- 
ception of the medulla oblongata; divided the vagus on 
both sides; and extirpated the lungs, with protection of 
the phrenic nerve. The breathing [efforts-C.] simply con- 
tinued for forty minutes after the excerebration," and con- 
tinues: "Had I not feared being influenced by theoretical 
considerations (later to be unfolded), I would say the in- 
spirations increased, soon after the removal of the lungs, in 
force and frequency, Any way, the motions were very 
energetic; the diaphragm was strongly contracted; the 18 
THE CAUSE OF RESPIRATION. 
thorax strongly raised. I repeated the research on sev- 
eral young dogs with the same effect. At bottom these 
experiments unfold nothing unawaited, for it has long 
been known that an excised head continues to breathe 
[make nasal movements-C.] for some time (in young 
rabbits I have observed this seventeen minutes after the 
beheading). 
"Thus one has occasion enough to believe that, with- 
out the accessory action of the vagus, an involuntary re- 
spiratory effort can take place." 
The striking thing about these passages to which I 
would call especial attention is the contribution they made 
and are held to have made to the improbability of the in- 
citation of respiration through the vagus; indeed, it would 
seem as though Dr. Meltzer, by citation of this experiment, 
wished to express his present coincidence with its express 
teaching, for he makes no objection to Volkmann's imme- 
di te conclusion. 
In explanation of the experimental result upon which 
his theory-if he still holds that theory-depends, Dr. 
Meltzer makes the statement that 1 ask for evidence that 
it was not due to dyspnoea from non-aeration of blood 
during the prolonged stoppage of respiration incident to 
his unusually strong excitations of the vagus. 
To this I object, as I have asked of him nothing that 
was not published in his original communication. 
I noted that he had not considered whether the inspi- 
ratory after-effect in question might be merely dyspnoea 
from vitiation of blood during the cessation of respiration. 
He now gives his reasons for his view. I believe, never- 
theless, that this after-effect of his stimulations of the vagus 
was dyspnoeic, and for the following reasons: First, any 
considerable simple cessation of respiration will produce 
dyspnoea as an after-effect; and, secondly, an expiratory THE CAUSE OF RESPIRATION. 
19 
position of the chest-i. e., a diminution in the volume of 
air still available within the pulmonary vesicles-will in- 
tensify such dyspnoea. But these conditions are essentially 
those of Dr. Meltzer's experiments. There is, however, a 
further similarity, and with reference to the vagus. In 
dyspnoea with unhindered respiratory passages, as upon 
marked muscular exertion, there must be, through the va- 
gus, owing to the increased mean distention of the chest 
(6), an increased stimulation of the inhibitory nervous 
mechanism at the center, which is, however, overcompen- 
sated for by the increased excitants in the blood, due to the 
muscular exertion. 
On the other hand, in a continuous stoppage of the res- 
piration by an electrical excitation of the vagus, there is, 
first, an obviously increased stimulation of the inhibitory 
mechanism, above that in the normal respiration. The ex- 
citation hereby may be quite weak. When its amount, 
however, is increased far beyond such point of sufficiency, 
as in very strong electrical excitations of the vagus, the 
stimulation of the inhibitory mechanism will be correspond- 
ingly increased ; for, as has been very fully shown by Bow- 
ditch, excitation of a nerve does not produce fatigue or ex- 
haustion on its part. The full effect of the same, therefore, 
must come upon the center, and exhaustion or fatigue may 
be expected to appear in the manifestations of the latter ; 
if not during such an excessive stimulation, at least upon 
its cessation. 
Dr. Meltzer does not inform us to what degree or what 
constancy of expiration his excitations led ; but he states 
that the effects are always expiratory when very strong cur- 
rents are used, while they are uncertain with weaker ones. 
From this we may conclude that antagonistic factors were 
present in his electrical excitations of the vagus, which 
would therefore probably render impossible a measurement 20 
THE CAUSE OF RESPIRATION. 
of the effect of such excitation upon the inhibitory mechan- 
ism of the respiratory center. 
That the effect upon the center, nevertheless, of strong 
excitation, particularly when prolonged, is itself strong may 
evidently be assumed ; that it must be lasting is shown by 
the fact that the normal inhibition outlasts the excitation, 
as shown by Gad (6). 
Secondly, during a stoppage of the respiration with con- 
tracted chest, the excitants of respiration in the blood rap- 
idly increase. 
So soon, then, in the case altogether, as the excessive 
excitation of the vagus is ceased, its stoppage plus the fa- 
tigue of the inhibitory mechanism will allow, and the in- 
creased excitants in the blood will therefore at once produce 
a very marked inspiratory after-effect. 
The conclusion, therefore, appears justified that the in- 
spiratory after-effect in Meltzer's experiments was dyspnoeic. 
In conclusion, I would bring together a denial on his 
part of my understanding of his main position, with those 
portions of his previous communication from which I ob- 
tained that understanding. He now says : " Dr. Cowl fur- 
ther objects to the inference I am supposed to have drawn 
from my experiments on the trunk of the nerve [vagus-C.], 
that the lungs themselves are likewise provided with respi- 
ratory nerve fibers, and that these fibers exercise their func- 
tion in ordinary breathing. On this point Dr. Cowl is mis- 
taken ; I did not draw any such conclusion from my experi- 
ments." 
On pages 8, 10, 12, and 13 of his previous communica- 
tion are the following paragraphs, in their order : 
" On the other hand, it is equally certain that, at least in a 
number of individuals, medium strong and weak stimuli can 
positively produce inspiratory effects. Let us for the present 
keep in view the latter individuals. For these, then, we are THE CAUSE OF RESPIRATION. 
21 
forced to assume that their vagi contain two kinds of fibers- 
those whose stimulation causes inspiration, and others whose 
stimulation inhibits inspiration." 
" But we can also conclude, wherever we find after an ex- 
piratory arrest an inspiratory after-effect, that inspiratory fibers 
are present in the trunk, and have been likewise stimulated in 
a latent manner." 
"But, as we have demonstrated in all animals under strong 
stimulation, such an inspiratory after-effect following an expira- 
tory inhibition, we may conclude that both kinds of nerves 
exist in the vagus of all animals." 
" According to the view above set forth, I believe I am able 
to formulate a theory of respiration which is free from both 
objectionable features. In the first place, I assume that both 
fibers-those producing and those inhibiting inspiration-equal- 
ly participate in the production of the rhythm. 
"But I do not assume that both kinds of fibers are excited 
by particular specific stimuli. I simply mean to introduce the 
long after-effect of the inspiratory fibers as a factor in the 
mechanism. We have above made it plausible enough that 
during strong stimulation of the trunk of the vagus, or during 
expansion of the lung [I], both kinds of fibers are equally ex- 
cited, and that in this the effect of the inhibitory nerves pre- 
dominates; but that after cessation of the stimulation the long 
after-effect of the inspiratory nerve is manifested precisely as 
in the cardiac nerves. Thus I believe that normal [! !] respira- 
tion, too, is effected according to the principle just explained. 
"Inspiration expands the lung [1!], thereby stimulating both 
the inspiratory and the inspiration-inhibiting nerve fibers." 
A comment upon these passages seems to me unneces- 
sary. I would merely offer them as an excuse for not dis- 
cussing his other remarks. 
Deferences. 
1. Marshall Hall. Memoirs on the Nervous System. London, 
1837. 
2. Schwartz. Die vorzeitige Athembewegungen. Ein Bei- 22 
THE CAUSE OF RESPIRATION. 
trag zur Lehre von den Einwirkungen des Geburtsactes auf der 
Frucht. Leipsic, 1858. 
3. Miescher-Riisch. Zur Lehre der Athembewegungen. Du 
Bois Reymond's Archie, 1885. 
4. B. S. Schultze. Der Scheintod Neugeborener. 
5. Cohnstein und Zuntz. Weitere Untersuchungen zur Phy- 
siologic des Saugethierfoetus. Pfliiger's Archie, Band 42, 1888, 
p. 342. 
6. Gad. Die Regulirung der normalen Athmung. Du Bois- 
Reymond's Archie, 1880, p. 1. 
7. Engstrom. Ueber die Ursache der ersten Athembewe- 
gungen. Skandinaeisch.es Archie fur Physiologic, II, 2 and 3, 
p. 158; also Centralblatt der Physiologic, Dec. 6, 1890, Band 
4, No. 18. 
8. A. Loewy. Experimentelle Studien uber das Athem- 
centrum in der Medulla Oblongata und die Bedingungen seiner 
Thatigkeit. Pfliiger's Archie, Band 42, 1888, p. 245. 
9. Gad. Ueber Athemreflexe von den Hauptbronchen nach 
Versuchen des Herrn Zagari. Verhandlungen der physiolo- 
gischen Gesellschaft zu Berlin, 1889-90. Sitzung 25 Juli, 1890, 
No. 18; also in Du Bois-Reymond's Archie, 1890. 
10. Traube. Gesammelte Beitrage, Bd. i, S. 293. 
11. Geppert und Zuntz. Ueber die Regulation der Athmung 
Pfliiger's Archie, Band 47, 1888. 
12. A. Loewy. Zur Kenntniss der Erregbarkeit des Athem- 
centrums. Pfliiger's Archie, Band 47, 1888, p. 601.' 
13. Rosenthal. Die Athembewegungen und ihre Bezieh- 
ungen zum Nereus Vagus. Berlin, 1862. 
14. Lehmann. Ueber den Einfluss von Alkali und Saure 
auf die.Erregung des Athemcentrums. Pfliiger's Archie, Band 
42, 1888. 
15. Gad. Ueber automatische und reflectorische Athemcen- 
tren. Verh. der physiolog. Gesellschaft zu Berlin, 1885-86, 
May 5, 1886, Nos. 7 and 8; also Du Bois-Reymond's Archie, 
1886. 
16. Kempner. Neue Versuche iiber den Einfluss des Sauer- 
stoflgehaltes der Einathmungsluft auf den Ablauf der Oxyda- THE CAUSE OF RESPIRATION. 
23 
tionsprocesse im thierischen Organismus. Du Bois-Reymond's 
Archiv, 1884. 
17. Marek wald. Die Athembewegungen und deren Inner- 
vation beim Kaninchen. Zeitschrift fur Biologic, 1886, p. 120. 
18. Volkmann. Ueber die Bewegungen des Athems und 
Schluckens mit besonderer Berucksichtigung neurologischer 
Streitfragen. Muller's Archiv fur Physiologic, 1841. JI REASONS WHY 
Physicians Should 
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