THE. INFLUENCE 
ANAESTHETICS 
ON THE 
VASO-MOTOR CENTRES. PHYSIOLOGICAL LABORATORY; HARYARD UNIVERSITY. 
THE INFLUENCE 
OF 
ANAESTHETICS 
ON THE 
YASO-MOTOR CENTRES. 
BY 
Assistant Professor of Physiology in Harvard University. 
HENRY P. EQWDITCH. M.D. 
AND i 
CHARLES SEDGWICK MINOT, B.S. 
Reprinted from the Boston Medical and Surgical Journal, May 21, 1874. 
BOSTON: 
PRINTED BY DAYID CLAPP & SON. 
IBU. THE INFLUENCE OP ANESTHETICS ON 
THE VASO-MOTOK OENTEBS.* 
The experiments reported in this paper were undertaken with the hope 
of contributing to our knowledge of the physiological action of anaes- 
thetics by investigating the effect of these agents on certain nervous 
processes, which find their expression in changes of the arterial blood 
tension. The anaesthetic used in most of the experiments was sulphu- 
ric ether, but, for the sake of comparison, experiments with chloroform 
were also instituted. 
As far as regards their power to produce insensibility to pain, anaes- 
thetics may be regarded as antagonizing the effects of irritation of 
sensitive nerves. It is interesting, therefore, to inquire how far this 
antagonism extends to other effects of the same irritation. One of the 
most constant physiological results of irritation of a sensitive nerve is 
a rise of arterial blood tension, due to a reflex stimulation, through the 
vaso-motor centres of the muscular walls of the smaller arteries, espe- 
cially those of the intestines. This phenomenon is so constant that its 
occurrence has been used as a test for the integrity of sensitive 
nerves, and a method of investigating the coui'se of sensitive nerve 
fibres in the spinal cord has been founded upon it.f 
Our first object was to determine the effect of anaesthesia on this 
reflex rise of blood tension. Since the contraction, reflex or voluntary, 
of the muscles of the trunk and limbs causes great irregularities in the 
blood tension, the phenomenon in question can be properly observed 
only when the possibility of such contraction is excluded. This can 
be most conveniently and effectually done by paralyzing the animal 
with curare, and keeping up life by artificial respiration. The experi- 
ments were, therefore, performed as follows. The animal (in most 
cases a dog) was confined upon the operating table in a supine posi- 
tion, and a dose of curare (varying, with the size of the animal, from 
two to ten cc. of a one-half per cent, solution) was injected into the 
external jugular vein. As soon as the respiratory movements ceased, 
the trachea was connected by means of a glass canula inserted into it 
with the apparatus for artificial respiration, which was so adjusted as to 
* Read before the Boston Society of Medical Sciences, February 24, 1874. 
f Miescher. Zur Frage der sensiblen Leitung im Rtlckenmark. Ludwig’s Arbeiten. 
1870. Page 172. 4 
imitate as closely as possible the normal respiratory rhythm. A canula 
was then placed in the carotid artery and connected with a mercury 
manometer carrying a pen, by means of which the blood tension was 
recorded on a long strip of paper, which was kept in uniform motion 
by clockwork. (The rate at which the paper moved was recorded by 
means of a pendulum, which broke an electrical circuit once a second, 
and thus, through an electro-magnet, moved a pen which wrote upon 
the surface of the paper.) 
The saphena nerve was then exposed and placed upon electrodes 
connected with the secondary coil of a Du Bois-Reymond induction 
apparatus, the primary current of which was supplied by one Grove 
cell. The irritation of the nerve was produced by closing the primary 
circuit by means of a key provided with a pen, which also wrote upon 
the paper directly under the pen recording the blood tension. The 
duration and the effect of the irritation could therefore be seen at a 
glance. 
After determining the effect on the blood-tension of irritation of the 
saphena nerve, which was invariably a rise, amounting, usually, to from 
thirty to sixty mm. of mercury, the tube of the respiration apparatus 
was connected with a bottle containing ether, in such a way that the 
air was forced into the lungs of the animal, mixed with the vapor of 
the anaesthetic. After the ether had been administered in this way 
for several minutes, the saphena nerve was again irritated, and the 
effect noted. The ether was then removed, the animal allowed to breathe 
pure air, and the nerve once more irritated in order to determine, by 
comparison with the effect of the first irritation, whether the nerve 
still retained its irritability. Between the periods of irritation, the 
nerve was removed from the electrodes and restored to its position 
amongst the tissues of the limb. One great obstacle to the successful 
performance of this experiment was the impossibility of determining 
when a sufficient amount of ether had been given to produce angesthe- 
sia, and when the effects of ether had been removed by breathing pure 
air ; for the relaxation of the muscles, the usual sign of complete 
anaesthesia, had already been produced by the curare. The want of 
constancy in the results, to be attributed, in part perhaps, to this 
difficulty, renders it undesirable to give minute details of the experi- 
ments. Suffice it to say that in the majority of cases the rise of blood 
tension consequent upon the irritation of the saphena nerve was less 
marked when the animal was under the influence of ether than when 
the anmsthetic was not used. Frequently, no great difference could 
be observed, and in one or two instances, especially at the beginning 
of the ether inhalation, the irritation of the nerve caused a more de- 
cided rise of tension than without the ether. Subsequent irritations, 
however, had generally a diminished effect, showing that, in this re- 
spect, the influence of ether developes itself slowly, and is, perhaps, 
preceded by a period of stimulation. These effects are shown by the 
curves represented in figures 1 to 11 inclusive.* These curves are 
traced directly from the records of the manometer, and, in studying 
them, it must be borne in mind that, owing to the mercury descending 
in one leg of the manometer as it rises in the other, the recorded varia- 
tions of blood-tension are only one-half the absolute variations. The 
curves are drawn from right to left, and the horizontal lines under 
* See explanation of figures at end of article. 5 
them indicate the time during which the irritation was applied to the 
nerve. The numbers over the horizontal lines indicate the intensity 
of the irritation in arbitrary units of the Du Bois-Reymond induction 
apparatus,* one Grove cell supplying the electrical current. The verti- 
cal column of figures on the right of each curve is a scale giving the 
absolute blood-tension in millimetres of mercury. 
Far more constant were the results obtained by the use of chloroform. 
Our experiments with this agent were not so numerous as those with 
ether, but the uniformity was sufficiently great to justify a conclusion 
as to its action. It was invariably found that, when an animal was 
under the influence of chloroform, irritation of the saphena nerve caused 
a much less marked rise of blood-tension than when the anaesthetic 
was not used. Sometimes there was absolutely no rise of tension to 
be observed, while at other times the rise was from one-third to one- 
half that produced by the same irritation on an animal not subjected 
to the action of chloroform. This effect is shown by the figures 12 to 
15 inclusive, which represent the results of irritations of the saphena 
nerve made alternately with and without chloroform. 
Now when the intensity of any reflex phenomenon is affected by the 
action of a drug, or any other external agency, this may take place in 
three different ways, viz.: through a change of irritability, either of 
the afferent or of the efferent nerves involved, or of the nervous centres 
through which the action takes place. It is, therefore, of interest to 
inquire in which of these three different possible ways chloroform di- 
minishes the reflex contraction of the bloodvessels consequent upon 
the irritation of sensitive nerves. This can only be determined by 
experiments in which one or the other of these three possibilities can 
be excluded. 
Now it was shown by Nawalichinf that compression of the two 
carotid arteries causes a great increase of blood-tension, due to an 
irritation of the vaso-motor centres, produced by the diminished sup- 
ply of blood sent to them. Our next object was, therefore, to deter- 
mine how a rise of blood-tension produced in this way is affected by 
chloroform inhalation. For this purpose, a dog was curarized, and 
kept alive by artificial respiration. The mercury manometer was con- 
nected with the crural artery, and the blood-tension recorded in the 
manner above described. The two carotid arteries were then exposed, 
and a thread placed loosely around each. At a given signal, the two 
threads were raised simultaneously, stopping the flow of blood through 
the arteries, and causing a very decided rise of blood-tension. Chlo- 
roform was then given, as in the former experiments, and the arteries 
again compressed. Little or no rise of blood-tension was now ob- 
served. This result is shown in figures 16 and 17, where the effects 
of compression of the carotids, both with and without chloroform, are 
given. Unfortunately, only one experiment of this sort was performed, 
but the result was so marked that wo may fairly conclude that the rise 
of blood-tension due to anaemia of the vaso-motor centres may be pre- 
vented by the inhalation of chloroform. Here the effect of the anaes- 
thetic must be to produce a diminished irritability, either of the vaso- 
motor centres or of the vaso-motor nerves, the third possibility above 
mentioned, viz., the diminished irritability of the sensitive nerves 
being, of course, excluded. It is, therefore, a reasonable inference, 
* The maximum intensity, i.e., with coils pushed together, being indicated by 1000. 
t Centralblatt far medicinische Wissenschaften. 1870. Page 483. 6 
in those cases where chloroform was found to diminish the reflex con- 
traction of the bloodvessels, that this effect was due not to any influ- 
ence upon the sensitive nerves, but to a diminished irritability either 
of the vaso-motor centres or of the vaso-motor nerves. Which of these 
two possibilities is the more probable is a question on which the ob- 
servations of Scheinesson* throw light. This observer found that, 
when an animal was under the influence of chloroform, no unusually 
strong irritation of the cervical sympathetic was necessary in order to 
cause a contraction of the vessels of the ear. In other words, the 
vaso-motor nerves had, under chloroform, preserved completely their 
normal functions. If, therefore, chloroform does not diminish the 
irritability of the vaso-motor nerves, then the effect of this anaesthetic 
in checking the rise of blood-tension consequent upon compression of 
the carotids or irritation of sensitive nerves, must be due to a dimi- 
nished irritability of the vaso-motor centres. 
Another very frequent, though not absolutely constant result of irrita- 
tion of sensitive nerves, is a diminished frequency of the heart-beats. 
This diminution begins usually soon after the blood-tension has reached 
its maximum, and continues often 20" or 80" after the irritation has 
ceased and the blood-tension has returned to its normal level. A slight 
and temporary acceleration of the heart-beats, coincident with the rise 
of blood-tension, not infrequently precedes this retardation. That this 
phenomenon is due to the influence of the vagus nerves on the heart is 
evident from the fact that after the section of these nerves no such re- 
sult is produced. This is proved by the tracings represented in figures 
18 and 19, showing the effects on the blood-tension and on the rate of 
the heart-beats of two irritations of the saphena nerve of equal inten- 
sity, applied one before and the other after section of the vagus nerves. 
It will be seen that after the section, though the blood-tension rises in 
consequence of the irritation of the sensitive nerves, the retardation of 
the heart-beats is absent. This retardation must, therefore, be due to 
an influence proceeding from the vagus centres along the vagus nerves 
to the heart. Whether this stimulation of the vagus centres is a direct 
effect of the irritation of sensitive nerves, or an indirect effect, conse- 
quent upon the rise of blood-tension, need not at present concern us. 
Our next object was to determine the effect of anaesthetics on this re- 
flex irritation of the vagus nerve. The experiments performed for this 
purpose were the same as those for determining the effect of anes- 
thetics on the reflex rise of blood-tension, for the quicksilver manome- 
ter records the heart-beats, as well as the blood-tension. It must be 
borne in mind, however, that the reflex rise of blood-tension is a far 
more constant phenomenon than the reflex retardation of the heart- 
beats, so that only a small proportion of the experiments made were 
available for the study of the latter question. The results of these ex- 
periments were not perfectly constant, but in the large majority of 
cases it was found that the inhalation of ether prevented the reflex 
retardation of the heart-beats from manifesting itself. In several 
cases, the irritation of the sensitive nerve caused a decided accelera- 
tion of the heart, the temporary and slight acceleration above alluded 
to as often occurring without ether, becoming under ether a more 
marked and prolonged effect. This is to be seen in Figs. 20 to 22 in- 
* Centralblatt far medicinisctie Wissenschaften. 1869. Page 506. 7 
elusive, showing the effect of irritation of the saphena nerve before, 
during and after ether inhalation. 
The experiments with chloroform were not conclusive, inasmuch as 
the phenomenon in question did not manifest itself distinctly in the 
cases where this anaesthetic was employed. 
Our experiments enabled us to study the direct effect of chloroform 
and ether on the normal blood-tension and pulse rate, though this was 
not the object with which they were undertaken. In regard to the 
effect on the blood-tension, a great difference was noticed in the two 
anaesthetics. While the inhalation of chloroform caused, invariably, a 
decided depression of the blood-tension, varying in the different ob- 
servations from 8 to 37 mm. of mercury ; ether, on the contrary, 
caused, in the majority of instances, a marked rise of tension, varying 
from 9 to 51 mm. of mercury, and in those cases where the tension 
seemed to be lowered by ether, this depression was never greater than 
6 mm. of mercury. This same difference between the two anaesthetics 
was observed by the committee appointed by the Royal Medical and 
Chirurgical Society to inquire into the uses and the physiological, 
therapeutical and toxical effects of chloroform.* The conclusion of 
the committee, however, that the diminished blood-tension under chlo- 
roform is due to an enfeebled action of the heart, cannot be accepted 
as expressing the whole truth, for a lowered blood-tension may also 
be caused by a diminished activity of the vaso-motor centres, and the 
experiments of Scheinesson above referred to render it probable that 
chloroform acts in both of these ways. 
No positive conclusions as to the effect of anaesthetics on the pulse 
rate can be drawn from our experiments. Chloroform caused, in some 
cases, an acceleration, in others a retardation of the pulse. The effect 
of ether was likewise variable. The recorded observations of Schei- 
nesson and of the committee of the Medical and Chirurgical Society 
are also at variance with each other on this point. The question can 
only be settled by new investigations directed particularly to this 
subject. 
In experiments like those above described, where the effects of suc- 
cessive nervous irritations arc to be compared, it is, of course, of the 
greatest importance that the method of stimulation should be such as 
to secure the greatest possible uniformity. The Grove’s element, and 
the sliding induction coil of Du Bois-Reymond, leave nothing to be 
desired as far as constancy and convenience in the production of elec- 
tricity are concerned; but, in the application of the electrodes to the 
nerve, certain difficulties are met with. If the nerve is allowed to lie 
upon the electrodes during the interval, often several minutes in dura- 
tion, between two successive irritations, there is great danger of its 
losing its irritability by drying and stretching. On the other hand, if 
the nerve is removed from the electrodes and restored to its normal 
position among the tissues, it is Impossible to replace it upon the 
electrodes with perfect certainty that it rests upon them in precisely 
the same way as during the previous irritation. Of these two sources 
of error, the latter is probably the lesser, and the nerve was accordingly 
in our experiments always restored to its place among the tissues 
between each two irritations. In view, however, of the difficulties in- 
herent in this method of experimenting, it would be unwise to regard 
as conclusive any results except those of the most positive kind. 
* Meclico-Chirurgical Transactions, vol. 47, p. 323. London. 1864. 8 
We must, therefore, content ourselves with presenting the following 
conclusions, as possessing, at most, only a high degree of probability : 
I. Chloroform inhalation lowers the reflex irritability of the vaso- 
motor centres, thus diminishing the power of an irritation of sensitive 
nerves to cause a rise of blood-tension. 
11. Ether acts, if it acts at all, much less powerfully, in this respect, 
than chloroform. 
In other words, while ether and chloroform resemble each other in 
their effect on those nervous centres whose activity is connected with 
the conscious perception of pain, the latter acts much more strongly 
than the former upon those centres which regulate the arterial blood- 
tension, and thus affects profoundly the conditions of animal life. 
Ether and chloroform are, therefore, both anaesthetics, but chloroform 
is, also, something more. 
To complete this study of the comparative action of ether and chlo- 
roform, many other experiments are needed, both to confirm the re- 
sults already reached, and to settle new questions arising in the course 
of the investigation. The subject would not be presented in its pre- 
sent imperfect form, were it not that the departure of one of us for 
Europe has made it necessary to interrupt, for the present, the series 
of experiments. 
Explanation of Figures. 
Figs. 1 to 11 inclusive show the effect of ether inhalation on the rise 
of blood-tension, caused by irritation of sensitive nerves. 
Fig. 1, before ether inhalation. 
Fig. 2, after 2'15" ether inhalation. 
Fig, 3, after 4/20" ether inhalation. 
Fig. 4, 4/4:0" after removal of ether. 
Fig. 5, after 5/ ether inhalation. 
Fig. 6, after 8' ether inhalation. 
Fig. *l, 6' after removal of ether. 
Fig. 8, before ether inhalation. 
Fig. 9, after 4/40" ether inhalation. 
Fig. 10, after 10'30" ether inhalation. 
Fig. 11, 5'40" after removal of ether. 
Figs. 12 to 15 inclusive show the effect of chloroform inhalation on 
the rise of blood-tension, caused by irritation of sensitive nerves. 
Fig. 12, before chloroform inhalation. 
Fig. 13, after 3' chloroform inhalation. 
Fig. 14, 3'45" after removal of chloroform. 
Fig. 15, after 3'30" chloroform inhalation. 
Figs. 16 and 17 show the effect of chloroform on the rise of blood- 
tension caused by compression of the carotid arteries. 
Fig. 16, without chloroform. 
Fig. 17, during chloroform inhalation. 
Figs. 18 and 19 show the effect of section of the vagus nerves on 
the changes of pulse-rate caused by irritation of sensitive nerves. 
Fig. 18, before section of vagus nerves. 
Fig. 19, after section of vagus nerves. 
Figs. 20 to 22 inclusive show the effect of ether inhalation on the 
changes of pulse-rate caused by irritation of sensitive nerves. 
Fig. 20, before ether inhalation. 
Fig. 21, during ether inhalation. 
Fig. 22, after ether inhalation.