Reprinted from the American Journal of Physiology. 
Vol. II. — July i, 1899. — No. V. 
DIRECT AND REFLEX ACCELERATION OF THE 
MAMMALIAN HEART, WITH SOME OBSERVA- 
TIONS ON THE RELATIONS OF THE INHIBI- 
TORY AND ACCELERATOR NERVES. 
By REID HUNT. 
[Associate in Pharmacology, Johns Hopkins University.] THE 
American Journal of Physiology. 
VOL. II. 
JULY i, 1899. 
NO. V. 
DIRECT AND REFLEX ACCELERATION OF THE MAM- 
MALIAN HEART WITH SOME OBSERVATIONS ON 
THE RELATIONS OF THE INHIBITORY AND ACCEL- 
ERATOR NERVES.1 
By REID HUNT. 
[Associate in Pharmacology, Johns Hopkins University.\ 
CONTENTS. 
Part I. 
Page 
Experiments on the accelerator nerves 396-429 
Methods of investigation 396 
Tonic activity of the accelerators 397 
Effect of the section of the accelerator nerves upon the heart; resist- 
ance of the accelerator centres. Effect of the section of the accel- 
erator nerves upon the duration of systole and diastole and upon the 
conduction of impulses from auricle to ventricle 398-401 
Fatigue of the accelerator nerves 407 
Changes in the heart-beat. The localization of fatigue. Fatigue occur- 
ring in the heart as a result of stimulating the accelerators. Death 
from stimulation of the accelerators 407-421 
Relation of the vagi to the accelerators ; protective action of the vagi upon 
the heart 422 
Stimulation of the vagus after section of the accelerators. Stimula- 
tion of the accelerators after section of the vagi. Antagonism of the 
accelerator and inhibitory nerves in their effects upon the duration 
of systole and diastole. Mutual antagonism of the inhibitory and 
accelerator nerves in virtue of their tonic activity 422-425 
1 These experiments were performed in the Physiological Laboratories of the 
Johns Hopkins Medical School, and of the College of Physicians and Surgeons, 
New York ; a summary of some of the results obtained was presented at the meet- 
ing of the American Physiological Society in December, 1898, and published in 
the Proceedings of the Society (This-joumal, 1899, ii,p. ix.).' Reid Hunt. 
396 
Part II. 
Page 
Reflex acceleration of the heart 429~435 
The cause of reflex acceleration. The afferent nerves by which reflex accel- 
eration is produced 429 
On the manner in which reflex acceleration is produced 43S_45^ 
The duration of systole and diastole and the latent period when the heart 
rate is increased in various -ways. Reflex acceleration after section of 
the accelerators. Stimulation of sensory nerves after section of the 
vagi. Influence of the tonic activity of the accelerators upon reflex 
acceleration. Some influences affecting the condition of the cardio-in- 
hibitory centre. The afferent nerve fibres by which reflex acceleration is 
produced 452 
Part III. 
General consideration of results 458-469 
Functions of the accelerator nerves 45^ 
Rapid heart action of other than reflex origin 462 
Summary of results 469 
PART I. 
Experiments on the Accelerator Nerves. 
Methods of investigation. — Most of the experiments described in 
this paper were performed on dogs, although some were made on 
cats and rabbits; it is to the dog, however, that the conclusions 
drawn are intended to apply primarily. The animals were always 
thoroughly anaesthetized in some manner. Curare was also 
frequently given; in these cases an effort was made to prevent the 
animal’s temperature from falling during the experiment, either by 
warming the air (which was also saturated with aqueous vapor) or 
by keeping the animal on a zinc box filled with warm water. If 
during the course of an experiment the blood pressure became very 
low, intravenous injections of warm normal saline or of Ringer 
solution were frequently made; by means of such injections the 
blood pressure and heart rate could be kept near the normal for a 
long time, and results of value obtained from experiments which 
would otherwise have yielded none. 
The heart rate and blood pressure were recorded by the mercury 
manometer in the usual manner; the readings of the blood pressure 
given have been corrected for the weight of the solution of sodium 
carbonate used to prevent coagulation of the blood. In some experi- 
ments Hurthle’s spring manometers, connected either with an artery Acceleration of the Mammalian Heart. 
397 
or with a cannula passed into one of the ventricles, were extensively 
used. 
The accelerators were usually exposed by resecting the first rib 
and opening the pleural cavities; such a procedure allows of a much 
more thorough exposure of the stellate ganglia and their branches 
than does the longer and more difficult method described by 
Schmiedeberg. 
Full details of the individual experiments will be given through- 
out the paper. 
Tonic Activity of the Accelerators 
The views of physiologists seem to differ widely on the question 
whether the accelerator nerves are in a condition of tonic activity or 
not. In some of the leading English1 and German2 text-books on 
physiology the statement is made that these nerves are only occa- 
sionally, not continually, in a condition of activity. In other text- 
books both of physiology and of medicine and frequently in the 
writings of physiologists it is either stated explicitly that these nerves 
are usually in a condition of activity or the assumption is made that 
this is the case. Other authors again do not refer to the question 
at all. 
Apparently the basis for the statement that the accelerators are 
not in a condition of tonic activity is the work of the Cyons.3 t hese 
physiologists, unlike von Bezold, failed to find any decrease in the 
heart rate in experiments on rabbits as a result of the section of 
the spinal cord or of the extirpation of the inferior cervical and stel- 
late ganglia. The later investigations of Tschirjew,4 Stricker and 
Wagner,5 and of Timofeew,6 all agree in showing that these nerves 
1 Waller : Introduction to human physiology, 3d ed., 1891, p. 107. 
2 Landois : Lehrbuch der Phvsiologie des Menschen, 7th ed., 1891, p. 807. 
3 Cyon, M. and E. : Archiv f. Anat., Physiol., u. wiss. Medicin (Reichert and 
du Bois-Reymond), 1867, p. 406. 
4 Tschirjew: Archiv fiir Physiologie, 1877, p. 164. 
5 Stricker and Wagner : Sitz.-Ber. d. kais. Akad. d. Wiss., 1878, math.- 
naturw. Cl., 77, Abth. Ill, p. 111. 
6 Timofeew : Quoted in Centralblatt fiir Physiologie, 1889, p. 235. Timofeew 
did not observe any immediate effect upon the heart rate of cutting the accelera- 
tors ; about three days after the operation, however, slowing of the heart began, 
and seems to have been permanent. That no immediate slowing of the heart 
occurred in these experiments may have been due to a reflex diminution of the 
tonicity of the vagi (which of itself would lead to an acceleration) resulting from 398 
Reid Hunt. 
are usually in a condition of tonic activity in rabbits as well as in 
dogs; moreover E. v. Cyon himself, in a recent article giving the 
results of experiments performed for the most part upon rabbits, 
speaks as though he considers these nerves to be in a condition of 
tonic activity.1 
My own experiments, some of which have already been pub- 
lished,2 lead me to believe that the accelerators must be considered 
as almost always in a condition of tonic activity, in fact much more 
constantly so than the cardio-inhibitory nerves. 
So far as I know the only question in relation to the tonic activity 
of the accelerators discussed by previous writers is the effect of the 
section of these nerves upon the rate of the beat of the ventricle; 
this as well as some other problems will be discussed below. 
Effect of the section of the accelerator nerves upon the heart rate ; 
resistance of the accelerator centres. — I have very little to add to 
what I have said in my previous paper as to the effect upon the 
heart rate of cutting the accelerator nerves; in the large number of 
additional experiments which I have made, I rarely have found a 
case in which they were not in a condition of tonic activity. This 
was true whatever the drug used for anaesthesia, and when an- 
aesthesia was produced not by drugs but by section of the crura 
cerebri or by compression of the cerebrum; also whether the vagi 
were intact or had been divided. 
One criticism which may be made against some of the experiments 
upon the effect of cutting the accelerators should be referred to here. 
The operation necessary to expose thoroughly the accelerator nerves 
sometimes leads to a lowering of the mean blood pressure; since 
the work of v. Bezold3 and Tschirjew it has been generally believed 
that a low blood pressure acts of itself as a stimulus to the centre of 
the operation; I have referred to this point in a previous paper (Journal of experi- 
mental medicine, 1897, ii, p. 160). 
Hering (Archiv f. d. ges. Physiol., 1895, lx, p. 468) observed an increase in the 
heart rate to follow extirpation of the stellate ganglia (the vagi being intact) ; 
after a few days the rate returned partially to the normal. Subsequent section of 
the vagi caused but little increase in the heart rate. These results seem also to 
indicate a tonic activity of the accelerators, the acceleration immediately fol- 
lowing the operation probably being due to a diminution of the tonic activity 
of the vagi. 
1 von Cyon, E. : Archiv f. d. ges. Physiol., 1898, lxx, p. 242. 
2 PIunt : Journal of experimental medicine, 1897, ii, p. 158. 
3 von Bezold : Centralblatt f. d. med. Wissenschaften, 1866, pp. 819, 820. Acceleration of the Mammalian Heart. 
399 
the accelerator nerves.1 Unless this factor is taken into considera- 
tion the objection may be made that an abnormal stimulation of the 
accelerators by low blood pressure has been interpreted as tonic 
activity of the centre. There were however among my experiments 
many cases in which as a result of careful operation the blood pres- 
sure was high (probably very near the normal) when the accelerators 
were cut, and yet there was a very marked slowing of the heart. 
I he following figures from an experiment upon a rather small dog 
may serve as an illustration of this point: the blood pressure was 
130mm. of mercury, the heart rate 391- in 10 seconds; section of 
the accelerators on the right side caused the blood pressure to fall to 
122 mm., while the heart rate decreased to 26\ beats in 10 seconds; 
section of the accelerators on the left side caused no change in the 
heart rate, but the blood pressure fell to 95 mm. 
On the other hand I have in a few cases obtained results to which 
the above objection may properly be made. Occasionally an animal 
was found in which the accelerators seemed to be in a condition 
of maximum acceleration, that is, electrical stimulation of the nerves 
after their section did not cause the heart to beat more rapidly than 
it had been beating before their section; in all such cases the blood 
pressure was very low. An example of such an experiment will be 
given below. 
Section of the accelerator nerves in my experiments seldom led to 
a marked lowering of the blood pressure; hence the criticism can- 
not be made against these experiments which the Cyon brothers 
made against the work of von Bezold. Von Bezold cut the spinal 
cord and attributed the slowing of the heart which followed to the 
cutting off of the accelerator impulses; the Cyons attributed it to 
the fall of blood pressure resulting from the dilatation of the blood 
vessels of the abdominal organs when the spinal cord is divided. 
The resistance of the accelerator centre to influences which reduce 
or entirely abolish the irritability of other physiological centres is 
very marked. Thus, while the tonic activity of the cardio-inhibitory 
and of the vaso-motor centres is lowered by such drugs as chloral, 
chloroform, and ether, and by excessive amounts of curare, these 
drugs seem to have but little effect upon the accelerator centre. In 
1 Asp (Sitz.-Ber. d. sachs. Gesellsch.d. Wiss., math.-phys. Cl., 1867, p. 173) and 
Nawrocki (Beitrage z. Anat. u. Physiol., Festgabe fur C. Ludwig, 1874, p. 220), 
however, consider the acceleration in these cases to be due to a diminution of the 
tonic activity of the vagi. 400 
Reid Hunt. 
one experiment upon a dog, for example, after a very large amount 
of curare had been injected into a vein, the blood pressure fell from 
83 to 22 mm. of mercury, and section of the vagi and stimulation of 
their peripheral ends had no effect upon the heart rate; yet section 
of the accelerator caused the heart rate to decrease from 29 to 23 
beats in 10 seconds. In another experiment the blood pressure was 
27 mm.; section of the accelerators caused the heart rate to decrease 
from 36 to 261 in 10 seconds. The accelerators were also found to 
be in activity in an animal which had been under the influence of 
ether for five hours, and in others in which severe operations and 
great loss of blood had led to an extremely low blood pressure. In 
a few animals, however, the temperature of which had fallen very low, 
the accelerators were not found in tonic activity.1 
Although section of the accelerator nerves has seldom failed to 
cause a slowing of the heart, yet the extent of this slowing has varied 
widely in the different experiments; in exceptional cases the rate 
after their section has been but one half or less than the previous 
rate. To what extent the variability of the results was due to 
differences in individual animals and to what extent to other causes 
it is impossible to state. In the case of the inhibitory fibres to the 
heart it is not difficult to determine the influences (drugs, etc.) which 
increase or diminish their tonus, and in the same animal this tonus 
may vary within wide limits in short periods of time; in fact 
the cardio-inhibitory centre seems to be in a condition of very 
unstable equilibrium. The tonus of the accelerator nerves is not so 
easily affected; I have been unable to find any constant relation 
between such factors, e. g., as the degree of anaesthesia, the condition 
of the blood pressure and of the respiration, etc., and the extent of 
the tonus of the accelerators, nor do I know of any grounds for sup- 
posing that this tonus undergoes changes comparable to those of the 
cardio-inhibitory centre. There are, moreover, indications that the 
condition of the heart itself plays a very important part in determin- 
ing the effect of cutting the accelerators; it is even probable that 
1 The resistance of the peripheral endings of the accelerators is also remark- 
able. Thus stimulation of the spinal cord in the cervical region has caused a 
marked acceleration of the heart, although, as a result of excessively large doses of 
curare, the blood pressure was not affected. In the last stages of asphyxia, also, 
stimulation of the accelerators is effective, as has already been described by 
Bowditch. Even when the heart is dying and the ventricles have ceased to beat, 
stimulation of the accelerators will sometimes cause the latter to begin again. Cold, 
however, diminishes the irritability of the accelerators, as was observed by Baxt. Acceleration of the Mammalian Heart. 
401 
changes in this organ are of more weight in this connection than 
changes in the accelerator centre. 
Effect of section of the accelerator nerves upon the duration of systole 
and of diastole. —The duration of systole and diastole was deter- 
mined in the manner described by Hurthle1 from the curve of 
carotid pressure recorded by the spring manometer. As this 
method will be referred to frequently in later parits of this paper a 
few words will be said about it here. Hurthle has shown that when 
tracings are taken with his manometers from the cavity of the left 
ventricle and from the aorta simultaneously the time elapsing 
between the appearance of the primary and the dicrotic waves of 
the aortic pulse curve is almost the duration of systole as deter- 
mined from the curve of intraventricular pressure. Of course 
these curves do not coincide in time; the primary elevation in the 
curve of aortic pressure does not appear until after the beginning of 
the systole of the ventricle and the dicrotic wave does not appear 
until a short time after the end of the systole. The former period, 
that is, the time elapsing between the beginning of the systole and 
the occurrence of the primary elevation on the curve of aortic pres- 
sure, corresponds to the time during which the intraventricular 
pressure is rising, but is not high enough to force open the semi- 
lunar valves (the Anspannungszeit) ; the latter period corresponds 
to the interval which elapses between the closure of the semi- 
lunar valves and the appearance of the dicrotic wave. Hurthle 
found in a number of observations that these two periods were 
almost of equal length, and that therefore the duration of systole can 
be determined directly from the curve of aortic pressure by measur- 
ing the time interval between the primary and the dicrotic wave. 
He suggests that the duration of systole and diastole can be deter- 
mined in a similar manner from the curves obtained by his manom- 
eter from other large arteries. 
I have made use of the above method for determining the duration 
of systole and diastole in a number of experiments. A Hurthle 
spring manometer was connected with one of the carotids and the 
pulse recorded upon the smoked paper of a Hurthle kymograph; 
the speed of the latter was ioomm. per second. A cannula was 
also connected with the femoral artery and the blood pressure 
recorded by a mercury manometer in the usual manner. In a 
number of experiments records of intraventricular and of aortic 
1 Hurthle : Archiv f. d. ges. Physiol., 1891, xlix, pp. 65-67. 402 
Reid Hunt. 
pressure were taken simultaneously, a spring manometer being 
connected with a catheter which had been passed down one carotid 
into the left ventricle,1 while a second manometer was connected with 
the other carotid. Comparison of the curves obtained in this manner 
sometimes showed a somewhat greater discrepancy than was to be 
expected from Hurthle’s description; still the differences were so 
slight that the error could as a rule be disregarded. 
One difficulty in using the above method for determining the 
duration of systole and diastole should be mentioned : it not un- 
frequently happens that after some change in the heart rate or blood 
pressure (such, for example, as that following stimulation of the 
cardiac nerves) the dicrotic wave of the curve becomes so indistinct 
as to make exact measurements difficult or impossible. Most of 
the experiments, however, or at least parts of most of the experi- 
ments, gave very satisfactory results. 
'The following experiment shows the effect upon the duration of 
systole and diastole of cutting the accelerator nerves. 
Experiment C. — Small dog, anaesthetized by sulphate of morphine and 
ether; curare. Stellate ganglia exposed. Left femoral artery connected 
with mercury manometer ; left carotid with Hurthle’s spring manometer. 
Duration in 
Blood 
Time. 
Heart beats in 
seconds of 
pressure 
Hr. min. 
sec. 
io seconds. 
systole 
diastole 
mm. 
1 23- 
0 
30 
0.165 
0.165 
46 
10 
Branches of 
1. stellate 
ganglion cut. 
24- 
0 
291 
0.165- 
0.170 
46 
30- 
0 
28+ 
0.160- 
0.190 
42 
32- 
0 
28 
0.160+ 
0.185 
34 
10 
Branches of 
r. stellate 
ganglion cut. 
20 
28- 
0.160+ 
0.180 
25 
0.165 
0.195 
30 
26+ 
0.175 
0.195 
33 
0 
0.205 
0.225 
30 
214 
0.230 
0.245 
34 
204 2 
0.235+ 
0.270- 
32 
35 
0.250 
0.270+ 
31 
1 A silver male catheter was found most convenient for this purpose. 
2 The maximum heart rate caused by stimulation of the accelerators in this 
experiment was 31 beats in 10 seconds, i. e., but very slightly greater than the 
heart rate before the nerves were divided. This was, therefore, one of the cases 
in which the accelerators were in a condition of almost maximal acceleration when 
they were cut. Acceleration of the Mammalian Heart. 
403 
The results obtained in the above experiment are better expressed in the 
form of a curve (Fig. i) in which the ordinates represent the duration in 0.05 
of a second of the systole and diastole of a single heart-beat at the end of 
each thirty seconds and the abscissae represent periods of thirty seconds. 
Parts of the tracing taken with 
the Hurthle manometer are re- 
produced in Fig. 2. 
Inspection of the above table 
and curves shows that in this 
experiment section of the accel- 
erators caused both systole and 
diastole to be prolonged, the 
prolongation of the former be- 
ing relatively (z. e. as compared 
with the previous rate) slightly greater than that of the latter. In 
nearly all of my experiments results similar to these were obtained; 
usually however the prolongation of the systole, though a con- 
Figure 1. Experiment C. Accelerator nerves 
cut at x. S shows the duration of systole, 
D that of diastole in 5 hundredths of a 
second. The abscissae represent periods 
of 30 seconds. 
Figure 2. Two thirds the original size. Experiment C. Upper tracing before, lower 
tracing 2 minutes after, section of accelerators on right side. Time in intervals of 
0.2 and 0.01 seconds. 
stant result of cutting the accelerators, was not so marked as in 
this case. 
The above experiment and the one quoted on p. 399, illustrate a 
point which I discussed in my earlier paper, namely, that section of 404 
Reid Hunt. 
the accelerator nerves on the right side usually causes a more marked 
slowing than section on the left side.1 
Effect of section of the accelerator nerves upon the conduction of im- 
pulses from auricle to ventricle. — At least two experiments have been 
described which tend to show that the accelerator nerves contain 
fibres which affect especially the conduction of impulses from auricle 
to ventricle.2 Certain observations have led me to think that these 
fibres are, under some circumstances at least, in tonic activity; or 
Figure 3. Two fifths original size. Ex- 
periment J. Curve of blood pressure 
before the accelerators were cut. B L, 
line of atmospheric pressure. Time in 
intervals of one second. 
Figure 4. Two fifths original size. Part of 
the curve of Experiment J following 
Figure 3. Taken minutes after the 
branches of the right stellate ganglion 
were cut. 
perhaps it would be better simply to say that the tonic activity of 
the accelerators affects the conduction of impulses from auricle to 
ventricle as well as the rate of the heart. 
The following is one of a number of experiments from which this 
conclusion is drawn. 
1 In most of my experiments in which the accelerators were stimulated on both 
the left and right sides, the latter caused greater acceleration than the former. 
Strieker and Wagner (op. cit., p. 109) made the same observation, but Frangois- 
Franck (Travaux du laboratoire de Marey, 1878-1879, iv, p. 83) failed to find any 
such differences in all but two of his experiments,—in these stimulation of the 
right accelerators caused a greater effect. These observations show that the dis- 
tribution of the nerves varies in different individuals ; but from my experiments I 
am convinced that, as a rule, more accelerator fibres pass to the heart on the right 
than on the left side. 
2 Bayliss and Starling : Journal of physiology, 1892, xiii, p. 407 ; Hunt and 
Harrington : Journal of experimental medicine, 1897, ii, p. 725. In the present 
series of experiments I have often observed results similar to those described by 
Bayliss and Starling, namely, that stimulation of the accelerators after these nerves 
had been stimulated a number of times caused an acceleration of the auricles, but 
that the ventricles frequently failed to follow all of the auricular beats. Acceleration of the Mammalian Heart. 
405 
Experiment J. — Bitch, weighing 22.5 kilo. Anaesthesia produced by 4.8 
grams acetone chloroform (trichloride of acetonic acid) and a little ether. 
Curare. Vagi cut. A catheter had been passed down one carotid into the 
left ventricle and a record of intraventricular pressure taken. The right stellate 
ganglion and its branches were exposed. The blood pressure was 57 mm. of 
mercury; the pulse rate 30 in 10 seconds. 
The accompanying curves (Figs. 3 and 4) show the effect upon 
the heart rate of cutting the accelerator nerves on the right side. 
The heart had been beating very regularly before the accelerators 
were cut; soon after they were cut there began to appear, occasion- 
ally, beats of unusual length. The number of these long beats in- 
creased very rapidly until finally there were periods of several seconds’ 
duration in which the heart was beating at but one half its previous 
rate. The record of intraventricular pressure showed that this irreg- 
ularity of the heart resulted from the “ dropping ” of some of the 
ventricular beats; that is, the duration of one of these long beats 
was just twice that of a normal beat. In some cases there was a 
slight, sudden rise of short duration of the intraventricular pressure 
during these long beats; this probably was due to the auricular 
beat.1 
The vagi had been divided in this experiment so that the change 
in the heart rate cannot be regarded as a reflex effect nor can it be 
attributed to changes in the blood pressure, for none occurred. 
The auricular beats were not recorded, and therefore the follow- 
ing explanation of this irregularity cannot be considered as estab- 
lished with absolute certainty. But all observations seem to agree 
in showing that the ventricle when it suddenly begins to beat at one 
half its previous rate is responding to but every second auricular 
beat; the most probable explanation of the cardiac irregularity in 
the above experiment would seem to be that section of the acceler- 
ators had caused a diminution of the irritability of the muscle fibres 
connecting the auricle and ventricle. Of course another explanation 
may be offered, namely, that section of the accelerators had simply 
diminished the irritability of the ventricle so that it was unable to 
respond to all the impulses reaching it from the auricles. I think 
however that in the light of the work of Gaskell, MacYVilliam, and 
Bayliss and Starling upon the conduction of impulses from the 
auricle to the ventricle, the former explanation is the more probable. 
1 Cf. Hurthle: Archiv f. d. ges. Physiol., 1891, xlix, p. 55. 406 
Reid Hunt. 
In other experiments upon dogs and cats and in one upon an 
opossum similar irregularities of the heart occurred after section of 
the accelerators, but as a rule they were less marked than in the ex- 
periment just described; in some, for example, a ventricular beat was 
dropped only occasionally. It is interesting that in all these cases 
it was section of the accelerators on the right side which led to these 
irregularities. 
Inasmuch as the mammalian heart will continue under proper 
conditions to beat with great regularity for hours after it is entirely 
separated from the central nervous system, the question may be raised 
why in the above experiments section of the accelerators caused it to 
beat irregularly. It is quite probable that in these cases the irritabil- 
ity of the heart had been decreased in some manner to such an ex- 
tent that the stimulus afforded by the accelerators was necessary to 
maintain regular cardiac action. In experiment J, for example, there 
were a number of influences which may have affected the heart. 
Thus the anaesthetic employed, acetone chloroform, seems to cause 
a loss of irritability of the heart, for in animals to which this drug has 
been given the heart rate is usually slow and the beat weak 1 after 
section of all the cardiac nerves; moreover, the blood pressure was 
low and perhaps the heart had been injured by the sound passed into 
the left ventricle. 
In the other experiments also in which section of the accelerators 
led to cardiac irregularity there were conditions which make it prob- 
able that the irritability of the heart was abnormally low. 
If the explanation offered above is the correct one, we should 
expect stimulation of the accelerators to cause the cardiac irregular- 
ity to disappear, especially as Bayliss and Starling2 have shown that 
stimulation of these nerves makes the transmission of impulses from 
auricle to ventricle more easy; as a matter of fact electrical stimula- 
tion of the accelerators not only caused an increase of the heart rate 
but an entire disappearance of the irregularity. The latter also 
followed the intravenous injection of hot normal saline solution, an 
agent which undoubtedly increases irritability of the heart. 
It is also interesting to note that in some of the exceptional cases 
in which section of the accelerators showed that they were not in tonic 
activity the heart was irregular both before and after all the cardiac 
nerves were divided. 
1 The injurious action of acetone chloroform upon the heart may be due to im- 
purities which are usually found in specimens of this drug. 
2 Bayliss and Starling: Journal of physiology, 1892, xiii, p. 414. Acceleration of the Mammalian Heart. 
407 
From such observations and considerations as the above I think the 
conclusion may safely be drawn that at times the tonic activity of the 
accelerators is very important for the regular action of the heart. 
Fatigue of the Accelerator Nerves. 
The statement is frequently made that the accelerator nerves are 
not easily fatigued, but the only basis for this assertion with which 
I am acquainted is an observation by Bohm.1 This investigator 
stated that he had stimulated the accelerators for two minutes with- 
out observing any indication of fatigue and expressed a doubt as 
to whether they can be fatigued at all. When it is remembered 
that even in cases of maximal acceleration the heart rate is rarely 
doubled, it does not seem reasonable to suppose that if any fatigue 
did occur it would be observed when these nerves were stimulated 
for so short a period as two minutes. 
That these nerves are not easily fatigued when subjected to a 
moderate stimulation follows from the fact that they are in a condi- 
tion of tonic activity; on the other hand it will be shown that fatigue 
may readily occur when the nerves are subjected to strong electrical 
stimulation. My experiments bearing on this point will be discussed 
in two parts; the first will be entirely descriptive, in the second an 
effort will be made to ascertain so far as possible where the fatigue 
occurs. 
Changes in the rate of the heart-beat. — When the accelerator nerves 
are stimulated continuously for some time (ten minutes for example) 
the heart does not remain long at the maximum rate but shows a ten- 
dency to return to the rate at which it was beating before the stimula- 
tion began. If these changes in the heart rate be expressed in the 
form of a curve in which the abscissae represent the time and the or- 
dinates the number of heart-beats in a given time (e. g. ten seconds) 
it will be found that as a rule the decrease in the heart rate occurs 
in two periods. There is first a comparatively rapid fall in the 
curve; this is followed by a much longer period in which the descent 
is very slight. Under some circumstances — these being determined 
by the condition of the heart and nerves, the character of the stim- 
ulus employed, etc.—the curve is continued in an almost straight 
line during the second period; in other words, the heart continues 
beating throughout this period at nearly a constant rate. The dura- 
1 Bohm: Archiv f. exper. Pathol, u. Pharmakol., 1875, iv, p. 275. 408 
Reid Hunt. 
tion of these two periods is very variable; occasionally they are 
absent altogether, there being in this case either no decrease at all in 
the heart rate (if the stimulation is of comparatively short duration) 
or the heart rate may decrease regularly; i. e., the curve becomes 
an almost straight line. 
The following experiment and curve show the usual result of 
stimulating the accelerators continuously for some time. 
Experiment 117. 
Small dog. Morphine 
and ether. Accelerators 
and vagi cut. The ac- 
celerators had been 
stimulated a number of 
times with results very 
similar to those shown 
in Fig. 5. 
Curves similar to 
the above are nearly 
always obtained when the accelerators are stimulated, whatever the 
condition of the heart or the strength or character of the stimulus 
employed. The same form of curve is also obtained in whatever part 
of their course the nerve fibres are stimulated, whether in the spinal 
cord, the rami communicantes, the annulus of Vieussens, or the 
small nerves running directly from the inferior cervical or the stel- 
late ganglion to the cardiac plexus. When the same nerve is stimu- 
lated a number of times in succession there is a gradual lowering 
of the height of the curve, but the form remains the same; the latent 
period also becomes longer with the successive stimulations. 
The above results recall those obtained when the peripheral end 
of the vagus is stimulated: in this case the heart, after a short 
period during which it is stopped or slowed, tends to return partially 
to its previous rate; it often reaches a constant rate, at which it 
continues to beat for hours.1 Martin2 found that when the isolated 
mammalian heart is warmed the beat is at first increased in frequency, 
but presently the heart returns partially to the former frequency and 
continues beating at this slower rate; in fact, if his results were 
Figure 5. Experiment 117. Stimulation of the accelerator 
nerves for minutes (x to x). The ordinates represent 
the number of heart-beats in 10 seconds; the abscissae 
periods of one minute. 
1 See Hough: Journal of physiology, 1895, xviii, p. 176; also Laulanie : 
Comptes rendus de des sciences, 1889, cix, P- 408. 
2 Martin: Physiological papers, 1895, P- io4- Acceleration of the Mammalian Heart. 
409 
expressed as a curve, the latter would have very nearly the same 
form as that obtained when the accelerator nerves are stimulated. 
Martin also called attention to the fact that similar changes in the 
heart rate are observed in some cases of fever — that is, the rate 
tends to return to the normal although the temperature remains 
the same. 
When the accelerators are stimulated in the course of a long 
continued stimulation of the vagus, the curve of fatigue is the same 
as when they are stimulated alone.1 
Effect of the strength of the stimulus upon the course of fatigue. — 
The effect upon the heart in any given case of stimulating the 
accelerators with currents of varying strength and rate seems to be 
determined largely by the condition of the heart and nerves at the 
time of stimulation. If the heart is vigorous and the nerves have 
not been stimulated often it may be said that in general the stronger 
the current, the longer continued is the phase of maximal acceleration ; 
if on the other hand the heart is not very vigorous or the nerves have 
been stimulated a number of times, fatigue occurs more quickly 
with a strong than with a weak current although the maximal rate 
reached by the heart may be the same in both cases. Also as a 
rule the stronger the stimulus the higher is the level at which the 
heart continues to beat during the stimulation. 
It is interesting that a slight initial decrease in the heart rate 
occurs when the accelerators are stimulated with a current too weak 
to cause a maximum acceleration; this resembles the “ escape ” ob- 
served by Hough when slight slowing was caused by stimulation of 
the peripheral end of the vagus. 
Effect of the rate of stimulation upon the fatigue of the accelerators. 
— The rate of the stimuli applied to the accelerators seems to have 
a greater effect upon the course of fatigue than does their strength. 
This was shown in many experiments in which the primary circuit 
of the du Bois-Reymond induction coil was interrupted by Ludwig’s 
Schlagwdhlcr or by an “ oscillating rod ” kept in vibration by an 
electromagnet; the number of stimuli per second could be varied 
within wide limits by either of these instruments. 
The following experiment shows how much more quickly fatigue 
is produced with a rapid rate of stimulation than with a slower 
rate. 
1 An experiment illustrating this is given on pages 174 and 175 of my article in 
the Journal of experimental medicine, 1897, ii. 410 
Reid Hunt. 
Experiment 137. — Dog. Morphine and ether. Curare. Spinal cord cut 
in mid cervical region. Branches of stellate ganglia divided. The result of 
stimulating the accelerators is shown in the following table. 
Time. Heart-beats 
Hrs. 
min. in io seconds. 
3 
41 
11 
R. annulus stimulated; 
14- 
primary circuit inter- 
21H- 
rupted 5+ times per 
201 
second ; secondary 
19- 
coil 13 cm. 
16* 
42 
i 
Stimulus off annulus. 
16* 
16*- 
16 * 
16 
3 
53 
R. annulus stim.; 2* 
12- 
stimuli per second; 
— 
secondary coil 13 cm. 
164- 
17- 
Time. 
Heart-beats 
Hrs. min 
. in io 
seconds. 
55 
Secondary coil 10 cm. 
174- 
204- 
56 
204- 
Coil 5 cm. 
— 
204- 
59 
20- 
Coil 0 cm. 
— 
20 
4 2 
20 
5 stimuli per second; 
— 
coil 0 cm. 
21- 
184- 
4 
17* 
17 
In the above experiment no diminution of the acceleration 
occurred when the accelerators were stimulated with 2\ stimuli 
per second, whereas 5-f- stimuli per second caused such a diminu- 
tion to occur very quickly. 
In almost every experiment there was found a rate at which the 
accelerators could be stimulated for some time with but little 
decrease in the acceleration. This, which may be called the opti- 
mum rate, varied greatly in different experiments and seemed to be 
determined by the condition of the heart and nerves. Thus in one 
experiment stimulation of the right annulus with an ordinary du Bois- 
Reymond coil in which the primary circuit was interrupted by the 
Neef hammer, caused the heart rate to increase from 23 to 29 beats 
in 10 seconds; but in the course of three minutes during which the 
stimulation continued the rate decreased to 24^-f-: after a few 
minutes’ rest the annulus was again stimulated but now the primary 
circuit of the coil was interrupted by the ScJilagwahler at the rate 
of 6 times per second ; the rate of the heart increased from 22 to 29.] 
beats in 10 seconds; after three minutes’ stimulation the rate was 29, 
showing that no fatigue had occurred. 
1 The dash (—) indicates that the heart-beats were not counted for io seconds. Acceleration of the Mammalian Heart. 
411 
Duration of systole and diastole in fatigue. — A number of experi- 
ments was made to determine whether both systole and diastole 
became longer when fatigue occurred in the course of a prolonged 
stimulation of the accelerators; it was found that they were longer, 
and that the prolongation occurred to about the same extent in 
both cases, so that the curve representing these changes were almost 
parallel. 
It is interesting to compare these results with those observed when 
the heart is “ escaping” during a prolonged stimulation of the vagus. 
When the peripheral end of the vagus is stimulated the diastole is 
always prolonged; as a rule the systole is also prolonged, but to a 
less extent; but while the diastole becomes shorter as the heart 
“ escapes ” to a more rapid rate, the systole remains about the 
same length throughout the stimulation. Thus during the “ escape ” 
of the heart from slowing as well as during the slowing caused by 
stimulation of the vagus it is the diastole which is most easily 
affected. On the other hand when the heart is slowed by section of 
the accelerators or when it is accelerated by the stimulation of these 
nerves or when fatigue occurs during their stimulation, both systole 
and diastole are affected; in fact, it seems almost as if one was 
affected through the other. If however the accelerators are stim- 
ulated when the heart is beating very slowly, as a result for 
example of stimulation of the vagus, then shortening of the diastole 
may occur before that of the systole ; this point will be referred to later. 
Local effects in the nerve. — It became evident very early in the 
investigation of the cause of the decrease in the heart rate during 
a prolonged stimulation of the accelerators that two factors are 
involved; first, a local action upon the nerve at the point stimulated, 
and, secondly, an effect upon the heart itself or upon the nerve end- 
ings in the heart. The latter effect is the more interesting in this 
connection, but it is necessary to consider the former or a serious 
error will be introduced into the experiment. 
Local effect tipon the nerve at the point of stimidation.— Howell1 has 
shown that when certain nerves, especially some of the non-medul- 
lated variety, are stimulated with the faradic current for some 
time there occurs a loss of irritability at the point of stimulation; 
he called this loss of irritability “ stimulation fatigue,” without how- 
ever expressing any opinion as to its real nature. 
1 Howell, Budgett, and Leonard : Journal of physiology, 1894, xvi, 
p. 311. 412 
Reid Hunt. 
This local effect of the current upon the nerve is easily demon- 
strated in the case of the accelerators. If the stimulating electrodes 
be held on one point of the nerve until the heart rate has begun to 
decrease and they then be moved a few millimetres nearer the heart, 
a second increase in the heart rate occurs; this, like the first acceler- 
ation, continues a short time and then the heart rate again decreases. 
This experiment may be repeated a number of times. 
The following experiment will serve to illustrate this point. 
Experiment iig. Dog. Morphine and ether; curare. Accelerators and 
vagi cut. Blood pressure 82 mm. 
Time. Heart-beats 
Hrs. min. sec. in io 
seconds. 
5 20 30 
Stimulation of r. an- 
00 
CO 
nulus begun ; sec- 
ondary coil 17 cm. 
40 
32+ 
21 
404- 
22 
3744- 
25 
32i 
26 
Electrodes moved 
31 
slightly. 
Time. 
Heart-beats 
Hrs. min. sec. 
in io seconds. 
26 20 
36 
27 
34i 
Electrodes 
moved 
slightly. 
20 
39+ 
28 
37i 
30 
34 
Electrodes 
moved 
slightly. 
20 
3S£ 
In the above experiment the electrodes were moved towards the 
heart, but the same result is obtained when they are moved farther 
away from the heart, — a fact which shows that the conductivity of 
the nerve fibres at the point of stimulation is not lost. 
If instead of moving the electrodes to a different part of the nerve 
after the acceleration has begun to decrease, the strength of the 
stimulating current suddenly be increased, the pulse rate may again 
be accelerated for a short time. By increasing the strength of the 
stimulus repeatedly at short intervals the heart may be kept beating 
at the maximal rate for some time. 
Effect of stimulating the accelerators in different parts of their 
course. — Howell has shown that it is in the non-medullated nerve 
fibres that this local loss of irritability most often occurs, while the 
medullated fibres are less subject to it. In view of these results it is 
of interest to compare the effects of stimulating the accelerator nerves 
in that part of their course in which they are medullated with those 
observed when they are stimulated at a point where they are non- 
medullated. According to the prevailing view, these nerve fibres Acceleration of the Mammalian Heart. 
413 
belong to the medullated variety while passing from the spinal cord 
through the rami communicantes to the stellate, inferior cervical, and 
perhaps other ganglia of the sympathetic system ; from these ganglia 
they are continued as non-medullated fibres to the cardiac plexus. 
According to this view, therefore, in order to compare the effects of 
stimulating the medullated and non-medullated accelerator fibres we 
have only to stimulate the spinal cord or the rami communicantes on 
the one hand and the small nerves passing from the annulus and the 
inferior cervical ganglion on the other. The annulus itself probably 
contains both medullated and non-medullated fibres. 
It has been already stated that the form of the curves of fatigue 
was the same in whatever part of their course the nerves were stim- 
ulated ; it is impossible in most of the experiments, however, to state 
whether the fatigue occurred in the heart or was a local effect upon 
the nerve, as at the time no special attention was given to this point. 
The following experiment indicates, however, that the local effect 
upon the nerves varies according to the part of the course in which 
they are stimulated. 
Experiment 125. Dog. Morphine and ether. Right accelerators cut. Vagi 
intact. 
The second thoracic ramus communicans had been stimulated a number of 
times, during and probably as a result of which the heart rate had decreased 
from 34 to 22 beats in io seconds. The right annulus was now stimulated for 
the first time, with the result shown in the following table. 
Time. Heart-beats 
Hrs. min. sec. in io seconds. 
12 40 30 22|- 
R. annulus coil 16 cm. 
26|+ 
35- 
35+ 
35+ 
41 30 31- 
42 27+ 
30 26J+ 
Time. 
Heart-beats 
Hrs. min. sec. 
in io seconds. 
43 
26J 
46 
25 
40 
Current turned to 2d 
ram. com. 
47 
36 
48 
34i4- 
49 
334- 
52 40 
30£ 
Thus during a stimulation of the right annulus continuing 6 min- 
utes the heart rate fell to 25 beats in 10 seconds, while during a 
stimulation of the ramus communicans of the same duration it fell to 
but 30-3- and this notwithstanding the fact that the latter nerve had 
been stimulated a number of times while the former was stimulated 414 
Reid Hunt. 
for the first time and that also a much larger number of accelerator 
fibres was doubtless stimulated when the current was applied to the 
annulus than when the ramus was stimulated. The explanation of 
the above difference is probably to be found in the fact that the nerve 
fibres in the ramus are medullated while many at least of those in the 
annulus are non-medullated.1 
There is also a difference in the rapidity with which the different 
accelerator nerve fibres recover their irritability after stimulation. 
Thus in the above experiment stimulation of the annulus after 20 
minutes’ rest caused an acceleration of from 23 to but 26 beats in 
10 seconds, whereas stimulation of the second ramus after a rest 
of 20 minutes caused the heart rate to increase to 35 in 10 seconds. 
Fatigue occurring in the heart as a result of stimulating the acceler- 
ators.— While the experiment described above shows that the de- 
crease in the heart rate occurring after a prolonged stimulation of the 
accelerators is due in part to a local action upon the nerve fibres at 
the point of stimulation, there is very clear evidence that the heart 
itself can be fatigued by excessive stimulation of these nerves. That 
the heart is not easily fatigued by stimulation of the accelerators 
follows from the fact that they are usually in a condition of tonic 
activity; it was also shown above that moderate electrical stimulation, 
especially stimulation with a weak, slowly interrupted current, does 
not easily cause fatigue. If, however, the electrical stimulation is 
excessive or often repeated, and especially if the heart has been 
subjected to injurious influences, distinct indications of fatigue in 
the heart2 occur, as will be shown below. It is very probable that 
1 Similar results were obtained in a few experiments in which the spinal cord 
and the accelerator nerves were stimulated ; most of these experiments, however, 
were complicated by an unexpected factor. In a number in which the spinal cord 
had been divided in the cervical region not only was the acceleration from stimula- 
tion of the cord and of the accelerators very slight, but fatigue occurred with 
extraordinary rapidity. The section of the cord seemed to reduce the irritabilitv 
not only of the accelerator fibres in the cord, but also of those in the annulus and 
the branches of the stellate ganglia. Munk and Schultz (Archiv fur Physiologie, 
1898, p. 307) have observed a similar loss of irritability in the phrenic nerve after 
section of the spinal cord ; one explanation which they suggest, with considerable 
reserve, is that the irritability of the nerve was affected by the changes in the cir- 
culation following section of the cord. It is doubtful whether this explanation 
would hold for the accelerators; for, as has been pointed out above, these nerves 
are not easily affected by changes in the blood pressure. 
2 The expression “fatigue in the heart” is meant to include either fatigue of 
the endings of the accelerator nerves or of the cardiac muscle, or of both ; it is by 
no means easy in many cases to distinguish between the two. Acceleration of the Mammalian Heart. 
415 
the same thing occurs whenever the accelerators are thrown into 
excessive action by causes originating in the body itself. 
Effect of repeated stimulations of the accelerators upon the pulse rate, 
irritability of the heart, etc. — After repeated stimulation of the accel- 
erators the pulse rate very often decreases. This decrease frequently 
occurs in cases where the vagi have been cut and therefore it can- 
not always be referred to an increased influence of the inhibitory 
nerves; nor can it in many cases be due to changes in the blood 
pressure or to a decrease in the animal’s temperature, for it takes 
place when no such changes occur. Moreover in many experiments 
no change in the heart rate occurs during periods of rest of the same 
duration as the periods of stimulation. From such considerations as 
these I think the conclusion must be drawn that the slowing of the 
heart following stimulation of the accelerators is due to fatigue of the 
heart itself. 
The following data may serve as an illustration of the extent to 
which the heart may be slowed as a result of repeated and long 
continued stimulation of the accelerators. The experiment was per- 
formed upon a dog anaesthetized by morphine and ether. After 
section of the vagi and accelerators the heart rate was 40+ in 10 
seconds. The accelerators were stimulated 39 minutes; soon after 
the stimulation the rate was 34 in 10 seconds and it remained at this 
level during the period of rest which followed the stimulation. After 
a second stimulation of the accelerators continuing 9 minutes the 
heart was beating at the rate of 28 in 10 seconds and continued at 
this rate during a period of 5 minutes’ rest. The nerves were now 
stimulated a third time. The stimulation continued only five min- 
utes, but after it the rate sank to 2l\. During this entire period 
the blood pressure had fallen very slightly, only about 10 mm. of 
mercury. 
Results similar to the above are often observed, but it is not always 
so easy to exclude factors other than that of the stimulation of the 
accelerators. 
That the irritability of the heart is lowered by long continued 
stimulations of the accelerators is shown by such an experiment as 
the following; the animal used was a dog anaesthetized by morphine 
and ether. Early in the experiment a small branch of the right 
annulus was stimulated for 20 seconds; the heart rate increased from 
20 to 33 in 10 seconds. The ventral limb of the right annulus was 
now stimulated for 21 minutes, the position of the electrodes upon 416 
Reid Hunt. 
the nerve being frequently changed. After the cessation of the 
stimulation the small branch of the annulus mentioned above was 
stimulated again with the same strength of current as before: the 
heart rate increased from 20 to but in 10 seconds. The only 
plausible explanation of the slight effect caused by the second stim- 
ulation of this small nerve is that the irritability of the heart had 
been diminished by the long continued stimulation of the annulus. 
Numerous other cases could be quoted in which stimulation of 
the annulus or of the small branches passing from the inferior cer- 
vical ganglion had but little effect upon the heart after repeated or 
long continued stimulation of the spinal cord or of those rami 
communicantes through which the accelerator fibres pass. 
Another indication that stimulation of the accelerators causes a 
diminution of the irritability of the heart is found in the study of 
the effects of the intravenous injection of extracts of the suprarenal 
gland. As is well known, the injection of such extracts into an 
animal in which all the cardiac nerves have been cut leads to a great 
acceleration of the heart-beat; in a number of my experiments the 
maximum rate reached after such an injection coincided almost 
exactly with the maximum rate resulting from stimulation of the 
accelerators. Small quantities of the extract may be injected a 
number of times in succession without any diminution of the effect. 
If, however, the accelerators be stimulated for some time with a 
strong current between two such injections, it is found that the 
second injection has less effect than the first one. Thus, early in 
one experiment stimulation of the right annulus caused an accelera- 
tion from 3i| to 40.} beats in 10 seconds, while the injection of an 
aqueous extract of the suprarenal of a dog caused the heart rate 
to increase to 39. The accelerators were now stimulated for about 
an hour, and then after a period of rest they were again stimulated 
for a short time; the result of the second stimulation was that the 
heart rate increased from 31 to 35.} beats in 10 seconds; the injection 
of the same quantity of the suprarenal extract as above caused the 
heart rate to increase to 35.1 
1 The interpretation of these results will depend upon the view held as to the 
action of suprarenal extracts upon the heart. If we accept the view of v. Cyon 
(Archiv f. d. ges. Physiol., 1898, lxxii. p. 371) that these extracts act upon the 
endings of the accelerator nerves, these experiments can only be regarded as evi- 
dence that the stimulation of the accelerators caused fatigue of the endings of 
these nerves; if, however, we adopt the view of Cleghorn (This journal, 1899, ii. 
p. 281), based upon experiments with the isolated apex of the dog's heart, that the Acceleration of the Mammalian Heart. 
417 
In another experiment suprarenal extract caused a marked accel- 
eration before the accelerators were stimulated; after the nerves 
were stimulated until they ceased to have any effect upon the heart 
another injection of the suprarenal extract was made, but with 
entirely negative results.1 At times on the other hand the injection 
of suprarenal extract seems to restore the influence of the accelera- 
tors over the heart. 
Two other results of repeated stimulations of the accelerators 
which probably indicate a loss of irritability of the heart may be 
mentioned: first, the latent period of acceleration is prolonged, and 
secondly, the after-effect of the stimulation is much less marked, i. e., 
the heart returns much more quickly to its previous rate after stimu- 
lation of the accelerators.2 This rapid return of the heart to the 
action of these extracts is upon the cardiac muscle itself, then I think my experi- 
ments can be regarded as evidence that the heart muscle is fatigued by stimulation 
of the accelerators. 
1 There are other points of similarity between the action of the accelerators and 
suprarenal extracts. Thus it has been my experience that when stimulation of 
the former from any cause failed to cause an acceleration of the heart, injection of 
the latter was also without effect. The effect of repeating the injections at short 
intervals is, moreover, very much like that of moving the electrodes slightly during 
a long continued stimulation of the nerves; after each injection, as after each 
shifting of the electrodes, there is a fresh increase in the heart rate. The heart 
can be kept beating at the maximum rate for some time in this manner. 
It is also interesting to note in this connection that it was impossible to obtain 
any summation of the effect of the maximal stimulation of the accelerators and of 
the injection of suprarenal extracts ; thus, when the injection was made simultane- 
ously with the stimulation, the maximum rate of the heart was no greater than 
when it was made alone or when the accelerators were stimulated alone. If, how- 
ever, the stimulus applied to the accelerators was sub-maximal, the injection of 
suprarenal extract would cause the heart rate to reach the same level as when the 
stimulus was maximal or when a considerable amount of extract was injected 
alone. There seemed to be a limit to the rate to which the heart could be accel- 
erated (just as in cases of Basedow’s disease, fever is said to cause no farther 
acceleration of the heart) ; in these experiments this limit was the same for the 
injection of suprarenal extract and for the electrical stimulation of the accelerators. 
It may be added that in one experiment injection of warm Ringer solution caused 
the same acceleration as did stimulation of the spinal cord and of the annulus. 
Bdhm states that in cats certain drugs cause a greater increase in the heart rate 
than does stimulation of the accelerators, and that therefore the acceleration of the 
latter case is not maximal; it should be noted, however, that these comparisons 
were not made upon the same animal. 
2 Bohm (Archiv f. exper. Pathol, u. Pharmakol. 1875, P- 275) made a similar 
observation, but did not offer any explanation of it. 418 
Reid Htint. 
previous rate is especially marked if the irritability of the heart has 
been reduced by the action of cold as well as by repeated stimulation 
of the accelerators. 
Stimulation of the vagus after repeated stimulation of the accelerators. 
— I think further evidence of fatigue occurring in the heart as a result 
of stimulating the accelerators is to be found in the comparison of 
the effects of stimulating the vagus before and after repeated stimula- 
tions of the accelerators. We know from the experiments of Hough 1 
(and I have had many opportunities of confirming his results) that 
the less vigorous the heart the greater is the effect of the stimulation 
of the vagus. Hence if stimulation of the accelerators does reduce 
the vigor of the heart we should expect to find the effect of the vagus 
increased after a long continued stimulation of these nerves; experi- 
ment shows this to be the case. This result is shown in a striking 
manner if, as was the case in the following experiment, the acceler- 
ators are stimulated during a prolonged stimulation of the vagus. 
Experiment of July 2d. Bitch. Morphine and ether; curare. Vagi and 
accelerators cut. The accelerators had been stimulated a number of times 
with the result that the maximum acceleration was less with each successive 
stimulation. The following table shows that the effect of the vagus became 
greater after stimulation of the accelerators. 
Time. 
Heart-beats 
Hrs. min. 
sec. in io seconds. 
4 22 
Stimulation of r. vagus 
40 
begun ; 13 stimuli 
per second; second- 
ary coil 0 cm. 
10 
27 
20 
23+ 
23 
Stimulation of r. annu- 
25 
lus begun; second- 
ary coil 17 cm. 
10 
32i 
20 
41 
30 
4H 
Time. 
Heart-beats 
Hrs. min. i 
sec. in io 
seconds. 
24 
364 
25 
Stimulus off annulus. 
31 
26 
244- 
4 26 
10 
24 
30 
21 
R. annulus stimulated 
secondary coil. 
; 
27 
10 
24J4- 
28 
Stimulus off annulus. 
234 
29 
Stimulus off vagus. 
18 
35 
38 
In this experiment the slowing of the heart caused by stimulation 
of the vagus became greater after each stimulation of the accelera- 
tors. That this was due to a change in the heart resulting from 
the stimulation of the accelerators is shown by the fact that when 
1 Hough : Journal of physiology, 1895, xviii, p. 162. Acceleration of the Mammalian Heart. 
419 
the vagus was stimulated alone the heart rate tended to return to the 
normal rather than to become slower; an indication of this tendency 
is shown in the first part of the above table. 
In another experiment very similar to the above, stimulation of 
the vagus caused the heart to be slowed from 27 to 1 beats in 
10 seconds; after a stimulation of the accelerators of but 28 seconds’ 
duration stimulation of the vagus caused the heart to be slowed to 
11 beats in 10 seconds. It should be added that in order to show 
the greater efficiency of the stimulation of the vagus after stimula- 
tion of the accelerators the former must follow the latter imme- 
diately, that is, the diminution of the irritability of the heart is of 
short duration unless the stimulation of the accelerators is continued 
for a long time. 
If the vagi are intact and in tonic activity the slowing following 
stimulation of the accelerators seems to be due in part to an increased 
influence of the vagi over the heart, for the slowing occurs much 
more quickly in experiments in which the vagi are intact than in 
those in which they have been divided. 
Such experiments as those just described seem to me to be of 
special interest and importance since they seem to show very clearly 
that stimulation of the accelerators causes diminished irritability of 
the cardiac muscle and not simply fatigue of the endings of the 
accelerator nerves; it is very difficult in most cases in which there 
are indications of fatigue in the heart to distinguish between these 
two possibilities. 
Effect of some drugs upon fatigue of the accelerators. — The results 
of a few observations which I have made incidentally upon the effect 
of two or three drugs upon the occurrence of fatigue from stimula- 
tion of the accelerators may be referred to here. 
After the intravenous injection of large doses of atropine and curare 
stimulation of the accelerators causes very rapid fatigue; whereas 
after the injection of sodium iodide 1 the fatigue is much less marked 
and the same is apparently the case after the injection of extracts of 
the suprarenal glands. 
The following experiment illustrates the effect of a large dose of 
curare and of the injection of sodium iodide. 
1 The use of sodium iodide was suggested to me by the work of Barbara (Archiv 
f. d. ges. Physiol., 1897, Ixviii, p. 436) and v. Cyon (Ibid., 1898, lxii, p. 176), who 
found that this salt acts as a powerful stimulus to the vasomotor and accelerator 
nerves; it also increases the irritability of these nerves while markedly lowering 
that of the vagi. 420 
Reid Hunt. 
Experiment 1J/.8. Dog. Morphine and ether. A very large amount of 
curare was injected into the femoral vein as a result of which the blood pres- 
sure had fallen from 83 to 20 mm. of mercury ; it rose later to 22 mm. The 
accelerators on the right side had been divided. The results are given in the 
following table. 
Time. 
Heart-beat in 
Blood 
Hrs. 
min. 
10 seconds. 
pressure. 
1 
50 
R. annulus stim. for 70 see.. 
21+ 
22 
coil 14 cm. 
33 
32 
30 
25i 
23 
(Record not good for 20 
? 
p 
seconds.) 
Stimulus off annulus. 
19 
53 
5.2 ccm. 20% sol. Nal in- 
20 
21 
jected into femoral vein. 
54 
R. annulus stim. as above. 
20 
191 
27 
32 
? 
2% 
29+ 
29+ . 
19 
1 
55 
29+ 
29+ 
• 
Stim. off annulus. 
27? 
26* 
56 
2S 
The experiment was continued for 25 minutes, during which the accelerators 
were stimulated a number of times with results very similar to the above, i. e., 
there were very slight indications of fatigue. 
The fatigue caused by stimulation of the accelerators is also less 
after the intravenous injection of warm Ringer solution; the accelera- 
tion is also greater. Thus in one experiment stimulation of the 
spinal cord, which had been divided in the upper cervical region, 
1 As a rule the injection of sodium iodide causes first a fall and then a rise of 
blood pressure ; that this did not occur in this experiment was probably due to the 
action of the very large dose of curare. A cceleraiion of the Mammalian Heart. 
42 I 
caused an acceleration from 19 to 25 beats in 10 seconds but this 
rate was maintained for but a very short time. After the intravenous 
injection of 400 c.c. of warm Ringer solution, which caused the blood 
pressure to increase from 27 to 61 mm. of mercury, stimulation 
of the cord caused an acceleration to 29 beats in 10 seconds and 
there was very little evidence of fatigue when the stimulation was 
continued for some time. Of course the greater efficiency of the 
stimulation of the accelerators may have been due in part to the 
higher blood pressure. 
A large amount of atropine suddenly injected into a vein causes 
the heart (or the endings of the accelerators) to be fatigued by 
stimulation of the accelerators almost as rapidly as did curare in 
the above experiment. 
Death from stimulation of the accelerators. — It happened not unfre- 
quently that death resulted from stimulation of the accelerators in 
these experiments. This usually occurred after a long experiment 
in which the accelerators had been stimulated repeatedly with strong 
currents or after the irritability of the heart had been reduced by 
the action of curare or of cold. Sometimes the ventricle suddenly 
went into fibrillar contractions either during or immediately after the 
stimulation of the accelerators, in other cases the heart-beats became 
slower and weaker until they were no longer recorded. 
An example of the latter mode of death is the following. 
Experiment 120. Small dog. Morphine and ether. A very large amount 
of curare was injected into the femoral vein, as a consequence of which the 
blood pressure fell to 27 mm. 
The results of stimulating the accelerators are shown in the following table. 
Time. 
Heart-beats 
Hrs. min. 
sec. 
in io seconds. 
3 45 
24| 
R. annulus stimu- 
lated; coil 14 cm. 
20 
37 
30 
38£ 
47 
33 
Time. 
Heart-beats 
Hrs. min. sec. 
in io seconds. 
48 
25 
50 
23- 
52 
20 
54 
12}- 
55 
12} 
56 
11 
The heart became so weak that the beat was not recorded ; it soon stopped 
altogether. 
Death caused by fibrillar contractions, together with the effect of 
cold on the heart, is well illustrated by the following experiment. 422 
Reid Hunt. 
Experiment 1J/.7. Small bitch. Morphine and ether. Vagi cut. A small 
opening was made in the pericardium and a considerable quantity of normal 
saline solution at about io° C. injected ; the heart was slowed slightly for a 
short time and then it returned to its previous rate (31 in 10 seconds). 
Time. 
Heart-beats 
Hrs. min. 
sec. in io seconds. 
3 54 
Branches of r. stellate 
31 
ganglion cut. 
15* 
55 
12 
12 
56 
Normal saline (10° C.) 
24 
injected into pericar- 
dial cavity. 
23 h 
57 
Branches of 1. stellate 
22|+ 
ganglion cut. 
Time. Heart-beats 
Hrs. min. sec. in io seconds. 
10 
23 
4 1 
23+ 
R. annulus stimulated; 
secondary coil 12 cm. 
24+ 
27 2 
30+ 
29+ 
28 
24 
Ventricles going into 
fibrillar contractions; 
auricles beating regu- 
larly. 
Death from stimulation of the accelerators frequently occurred 
with as much suddenness as in the above experiment, although in 
those cases in which the accelerators had been stimulated repeatedly 
the heart rate had as a rule decreased somewhat (from 28 to 19 in 
one experiment, for example). 
Sometimes the heart beat regularly and rapidly during a stimula- 
tion of the accelerators but died a few seconds after the stimulations 
ceased. 
The strength of the current used in these experiments in which 
death occurred was no greater than that used in other experiments, 
and the nerves were usually stimulated near the stellate ganglion ; it 
is very improbable therefore that death was due to an escape of 
current to the heart: it probably was due simply to the inability of 
the heart in its weakened and exhausted condition to respond to the 
demands made upon it by the stimulation of the accelerators. 
Relation of the Vagi to the Accelerators; Protective 
Action of the Vagi upon the Heart. 
Stimulation of the vagus after section of the accelerators. — In my 
previous paper I have called attention to two effects of the section 
of the accelerators upon the results of stimulating the vagi; (i) the Acceleration of the Mammalian Heart. 
423 
same stimulus applied to the vagus causes a greater slowing of the 
heart after the accelerators are cut, than before, and (2) the “escape” 
of the heart during a long continued stimulation of the vagus is less 
complete after the accelerators are cut. 
Other effects of the section of the accelerators in relation to the 
stimulation of the vagus will be described later in this paper; one 
other point may be mentioned here although I have but few experi- 
ments to quote. A number of physiologists 1 state that while stimu- 
lation of the accelerators causes a shortening of both systole and 
diastole, stimulation of the vagus causes a prolongation of diastole 
and as a rule but little effect upon the duration of systole. In com- 
paring the effects of stimulating the vagus in different experiments 
of my own I often have observed that in those cases in which the 
accelerators were intact and in tonic activity stimulation of the vagus 
had little effect upon the duration of the systole, while in those in 
which the accelerators had been cut a very considerable prolongation 
of systole frequently occurred. Thus in experiment C (see p. 402) 
after the accelerators were cut stimulation of the vagus caused 
the systole to be prolonged from 0.26 to 0.345 seconds or over 32 
per cent. 
Stimulation of the accelerators after section of the vagi. — T. he tonic 
activity of the vagi limits the effect of stimulating the accelerators ; this 
is shown in two ways. In the first place stimulation of the accelera- 
tors with sub-maximal stimuli has a greater effect upon the heart after 
than before section of the vagi if these are in tonic activity. 1 hus 
in one experiment stimulation of the accelerators with a weak current 
caused the heart rate to increase from 16 to 24 beats in 10 seconds 
when the vagi were intact; section of the vagi caused the heart rate 
to increase to 26} ; stimulation of the accelerators with the same 
strength of current as before caused the heart rate to increase to 34 
in 10 seconds. With very strong stimuli, however, the acceleration 
is the same before and after section of the vagi, for now the effect of 
the vagi is completely overcome and the heart is accelerated to its 
maximum rate. 
In the second place, the after-effect of stimulation of the accelera- 
tors is much more marked after section of the vagi; the heart returns 
more slowly to the previous rate. The following experiment illus- 
trates this point. 
1 Cf. Hurthle: Archiv f. cl. ges. Physiol., 1891, xlix, pp. 86-88 424 
Reid Hunt. 
Experiment 31. Large dog. Morphine and ether. Curare. Accelerators cut. 
Time. 
Heart-beats 
Hrs. min. 
sec. in 
io seconds. 
1 51 
20- 
R. annulus stimulated 
for 10 seconds; < 
:oil 
10 cm. 
224 
23|+ 
30 
19J+ 
55 
R. vagus cut. 
57 
30 
21+ 
Time. 
Heart-beats 
Hrs. min. sec. 
in io seconds. 
R. annulus stimulated 
for 10 seconds; coil 
10 cm. 
24 
28 
1 58 
26i 
23 
21+ 
30 
20k 
20 
Antagonism of the accelerator and inhibitory nerves in their effects 
upon the duration of systole and diastole. — I have shown elsewhere 
that, contrary to the view of Baxt, when the accelerators and vagi 
are stimulated simultaneously7, the effect upon the heart rate is 
determined by the relative strength of the two stimulating currents, 
and that for sub-maximal stimuli the result is approximately the 
arithmetical mean of the effects of stimulating the nerves separately.1 
Does this law of the antagonism of these nerves hold good for both 
systole and diastole? My experiments, which however have not been 
very7 numerous upon this point, indicate that this is the case. In 
such experiments as these it is necessary to use currents the strength 
of which can properly be compared with each other as regards their 
effect upon the heart; for while a relatively weak stimulation of the 
accelerators will cause a shortening of the syrstole, a stronger stimu- 
lation of the vagus is required to prolong this phase of the heart’s 
contraction, and on the other hand a stimulus which, when applied to 
the vagus, will cause a very great prolongation of diastole may, when 
applied to the accelerators, affect neither systole nor diastole. In 
order to cause a prolongation of the systole by stimulating the vagus, 
it is sometimes necessary to use a current strong enough to bring 
the heart to a standstill; then, as the heart escapes from this stand- 
still, the systoles are found to be prolonged. 
If we accept a suggestion that has been made,2 namely, that those 
1 Hunt: Journal of experimental medicine, 1897, ii, p. 171. These results 
have since been confirmed by v. Cyon (Archiv f. d. ges. Physiol, 1898, lxx, p. 244), 
Wertheimer (Journal of physiology, 1899, xxiii, supplement, p. 20), and at least 
the essential part of them by Frank (Sitz.-Ber. d. Ges. f. Morphol. u. Physiol., 
Munich, 1897, i), quoted from the Jahres-Ber. d. Physiol., 1898, vi, p. 64. 
2 Hurthle : Archiv f. d. ges. Physiol., 1891, xlix, p. 89. Acceleration of the Mammalian Heart. 
425 
nerve fibres which affect systole are different physiologically from 
those which affect diastole, the differences noted above may be ex- 
plained by supposing that one set of fibres is much more irritable to 
electrical stimulation than the other. 
Whatever the explanation, it is undoubtedly a fact that at times 
when the accelerators and vagi are stimulated simultaneously the 
systole may be shortened as greatly as when the accelerators are 
stimulated alone, while the duration of diastole may be either un- 
changed or even slightly prolonged.1 Such results as these do not 
prove, however, that these nerves are not purely antagonistic; they 
only show that when the effects upon the different phases of the 
cardiac cycle are considered, the strength of the currents were not 
comparable, and that in order to bring out the true relations it is 
necessary to consider the phases separately. If the accelerator and 
inhibitory nerves are stimulated with currents which when applied 
separately to the nerves cause changes in one or other of the phases 
which are comparable (i. e. neither stimulus must be a super-maximal 
one), the result is almost the exact arithmetical mean of the effect 
produced when the nerves are stimulated separately. 
It is very easy to pass the limits of strengths of current which are 
comparable, and then the accelerator or inhibitory influence will 
preponderate in the one or the other phase, just as it does when the 
entire cardiac cycle is considered and one set of fibres is stimulated 
with a relatively much stronger current than the other. 
The above considerations explain the cases in which one nerve 
gains the mastery in the one or the other phases of the heart’s action. 
The table on page 426, from one of my experiments, illustrates 
these points, and shows how perfect the antagonism of the accelera- 
tor and inhibitory nerves may be if care is taken to select stimuli of 
proper strength. 
Thus when the two nerves were stimulated together the influence 
of the acclerators predominated during systole and that of the vagus 
during diastole, but in each case the effect of the one nerve was 
diminished by that of the other. 
Mutual antagonism of the inhibitory and accelerator nerves in virtue 
of their tonic activity. — Since both the inhibitory and accelerator 
1 Frank {loc. cit.) obtained similar results, but seems (I have not seen the 
original paper) to have interpreted them as indicating that the antagonism of the 
accelerators and inhibitory fibres is not perfect when their effect upon systole is 
considered. 426 
Reid Hunt. 
Duration of 
Systole. 
Duration of 
Diastoie. 
Per 
cent. 
Before stimulation .... 
0.25" 
0.37" 
Vagus stimulated alone 
0.27" 
0.61" 
( Systole prolonged . 
\ Diastole prolonged 
8 
65 
Accelerators stimulated alone 
0.18" 
0.30" 
( Systole shortened . 
( Diastole shortened 
28 
19 
Both nerves stimulated . . 
0.22" 
0.45" 
( Systole shortened . 
( Diastole prolonged 
12 
21 
nerves are usually in tonic activity and are also antagonistic, it 
would seem to follow necessarily that the tonic activity of the one 
would limit the tonic activity of the other, so that the heart rate at 
any time (so far as it depends upon the cardiac nerves) is determined 
by the relative strength and number of the impulses reaching the 
heart from the central nervous system. In order to test this sup- 
position it is desirable to determine the heart rate (1) when both 
nerves are intact and in tonic activity, (2) when the heart is under 
the influence of the accelerators alone, (3) when it is under the 
influence of the inhibitory nerves alone, and (4) when both nerves 
are divided. Such an experiment can be performed by suspending 
the activity' of one of the nerves in such a manner that it can readily 
be restored again; this may easily be done by cooling the vagus. 
When the dog’s vagus is cooled to about o.° C., the power of the 
inhibitory fibres to conduct impulses is lost,1 but it can readily be 
restored by warming the nerve; this method was employed in a 
number of experiments, of which the following is an example. 
Experiment 153. Small bitch. Morphine and ether. Curare. Stellate 
ganglia carefully exposed. Vagi cooled by passing cold alcohol through 
metal tubes upon which the nerves lay. 
Time. 
Heart-beats 
Hrs. min. 
in io seconds. 
10 45 
174- 
Vagi cooled. 
48 
25 
53 
294- 
Vagi warmed. 
55 
16 
Accelerators cut. 
Time. 
Heart-beats 
Hrs. min. 
in io seconds. 
11 5 
16| 
12 
Vagi cooled. 
16 
19+ 
17 
Vagi cut. 
20 
18 
20J 
1 Howell, Budgett, and Leonard: Journal of physiology, 1894, xvi, p. 304. Acceleration of the Mammalian Heart. 
427 
These results may be expressed in the following tabular form : — 
Under the influence of both nerves the heart rate was 17-j- 
Under the influence of the accelerator nerves the heart rate was . . 29+ 
Under the influence of the inhibitory nerves the heart rate was ... 16 
After section of both nerves the heart rate was 20i 
This experiment shows very clearly that the acceleration following 
section of the vagi is due in part to the tonic activity of the acceler- 
ators, but it shows also that it is not due entirely to this factor, for 
section of the vagi still caused some increase in the heart rate after 
section of the accelerators. 
It follows from such experiments as the above that the extent of 
the acceleration following section of the vagi is determined not only 
by the condition of the cardio-inhibitory centre, but also by that of 
the accelerator centre. If the tonic activity of the accelerator centre 
is very great and that of the cardio-inhibitory centre small, section 
of the vagi will lead to but little increase in the heart rate. In the 
exceptional cases in which the accelerators are not in activity, the 
increase of the heart rate following section of the vagi is determined 
solely by the condition of the cardio-inhibitory centre. In some 
experiments the entire tonus of the inhibitory nerves seemed to be 
exerted in holding the accelerators in check; for while cooling of the 
vagi caused an acceleration of the heart when the accelerators were 
intact, after section of the latter nerves neither cooling nor section 
of the vagi caused any change in the heart rate. 
In a similar manner the extent of the slowing of the heart follow- 
ing section of the accelerator nerves is determined not only by the 
condition of the accelerator centres, but also by that of the cardio- 
inhibitory centre. 
That the normal heart rate is determined by the tonic activity of 
the cardiac nerves, can scarcely be doubted; 1 the varying effect 
of cutting all the nerves is strong evidence for this view. Thus after 
section of both the accelerator and inhibitory nerves one of three 
conditions results: (i) the heart rate is faster, (2) the heart rate is 
slower, or (3) the heart rate is the same as before the nerves were 
divided. Which of these three conditions results is determined by 
the relative strength of the impulses reaching the heart through 
the cardiac nerves. If the inhibitory impulses are the stronger, 
section of all the cardiac nerves causes the heart to beat more 
1 Cf. v. Cyon : Archiv f. d. ges. Physiol., 1898, lxx, p. 242. 428 
Reid Hunt. 
rapidly; if the accelerator impulses are the stronger, section of the 
nerves causes the heart rate to become slower. 
In many of the experiments described above it is evident that the 
vagi restrained the activity of the accelerators; 1 and so, since fatigue 
and decrease in the irritability of the heart result from the action of 
the latter nerves, the vagi acted as a protection to the heart. 
Moreover, there is evidence that, so far as the condition of the 
heart can be judged by its rate, stimulation of the vagus has a bene- 
ficial influence upon the mammalian heart, as Gaskell showed it to 
have in cold-blooded animals. Thus if the accelerators be intact and 
the peripheral end of one vagus (both vagi having been divided) be 
stimulated a number of times with currents of moderate intensity, the 
heart rate is frequently greater after than before the vagus was stim- 
ulated. This increase in the heart rate is not to be confounded with 
the acceleration which sometimes follows immediately after stimula- 
tion of the vagus, and which is due to the accelerator nerve fibres 
present in the. vagus or vago-sympathetic trunk; the former is of 
much longer duration than the latter, and seems to be due to an im- 
provement in the condition of the heart, as a result of which the 
impulses reaching this organ through the accelerator nerves become 
more effective. This effect of stimulating the vagus was well shown 
in an experiment upon a dog: the heart rate some time after section 
of the vagi was 33 in 10 seconds; the peripheral end of one vagus 
was stimulated with a weak, slowly interrupted induced current for 
25 minutes, short intervals of rest alternating with longer periods of 
stimulation; after the stimulation the heart rate was 42 in 10 seconds, 
and it continued at this rate for some time. Such changes in the 
rate did not occur during periods of rest of equal duration. 
Another illustration of the protective influence of the vagus over 
the heart is found in some experiments in which the vagus and 
accelerators were stimulated simultaneously for some time. Atten- 
tion was called above to the fact that when the accelerators were 
1 In a similar manner the tonic activity of the accelerators checks the action of 
the vagi; if the latter are thrown into activity reflexly, or if the nerves be stimu- 
lated directly, the effect upon the heart is less when the accelerators are intact; 
thus the accelerators prevent excessive action of the vagi, and so a long continued 
lowering of the blood pressure which might be injurious to the functions of some 
of the organs. Of course, if the stimulation of the vagi is excessive, as in asphyxia, 
for example, the effect of the accelerators may be entirely overcome, just as the 
effect of the tonic activity of the vagi may be entirely overcome by a powerful 
stimulation of the accelerators. Acceleration of the Mammalian Heart. 
429 
thus stimulated it happened frequently that after the stimulation 
the rate of beat was considerably less than it was before the stimu- 
lation, and this was considered to be due to fatigue in the heart. 
If, however, the vagus was stimulated at the same time as the accel- 
erators, the decrease in the rate after the stimulation ceased was, as 
a rule, much less, or did not occur at all. In other experiments, 
instead of stimulating the two nerves simultaneously the effect of 
stimulating the accelerators after a period of rest was compared with 
the effect of stimulating them after an equally long period of stimu- 
lation of the vagus; not only was the maximum acceleration greater 
in the latter case, but it was of much longer duration. It should be 
added that in order to obtain this result the stimulation of the accel- 
erators must follow that of the vagus immediately; if a short interval, 
even one of a few minutes, elapsed between the two stimulations, the 
result was the same as when the accelerators were stimulated after a 
period of rest. 
Finally, in most of the experiments in which death resulted from 
stimulation of the accelerators the vagi had been divided.1 
PART II. 
Reflex Acceleration of the Heart. 
The cause of reflex acceleration. — Many text-books of physiology 
allude to the possibility of reflex acceleration of the heart being pro- 
duced in two ways: (1) by diminution of the tonus of the vagus, and 
(2) by stimulation of the accelerator centres. Very few of those 
who have studied this subject, however, speak of the former possi- 
bility ; usually all cases of reflex acceleration are referred to stimula- 
1 Death of the heart also resulted sometimes from the intravenous injection of 
hot normal saline solution or of Ringer solution, and it seemed to occur much more 
frequently in those animals in which the vagi had been divided. One experiment 
of this kind was especially interesting. Before the vagi were divided a consider- 
able quantity of normal saline solution was slowly injected into the femoral vein 
from a fountain syringe ; the temperature of the solution in the syringe was 530 C., 
but it was probably several degrees colder when it entered the vein. The injection 
increased the rate of beat, but not markedly (from to beats in 10 seconds), 
and no bad effects were produced; on the contrary, the condition of the circulation 
seemed to be decidedly improved. The vagi were divided, and some time after- 
wards a much smaller amount of the same solution was injected. The temperature 
of the liquid in the syringe was now but 50° C.; the heart-beats, however, were 
increased to 47 in 10 seconds ; soon they could not be counted; the blood pressure 
fell and the dog died. 430 
Reid Hunt. 
tion of the accelerator nerve. This attitude is well illustrated by two 
of the most elaborate articles dealing with the innervation of the 
mammalian heart which have appeared within recent years — that of 
Roy and Adami,1 and of v. Cyon.2 
Roy and Adami describe reflex acceleration resulting from the 
stimulating of sensory nerves, and attribute it to a stimulation of the 
accelerator nerves; in fact, when studying the effect of these nerves 
upon the heart, these authors stimulated, as a rule, a sensory nerve 
instead of the accelerators directly, as they considered the reflex 
acceleration obtained in this manner to be equivalent to the effect of 
stimulating the nerves themselves. 
Von Cyon describes reflex acceleration following the stimulation 
of a number of afferent nerves, and seems to ascribe it in all cases to 
a stimulation of the accelerators. Thus stimulation of a third root 
of the depressor,3 which he has found in certain animals of different 
species, causes a reflex acceleration, and v. Cyon thinks that this 
shows that the nerve fibres of this root are connected in a special 
manner with the accelerator centre. It is worthy of note, however, 
that v. Cyon emphasizes the fact that in these experiments the vagi 
were intact, and in at least one experiment the vagus centre seemed 
to be in a condition of exaggerated activity as a result of the mor- 
phine used as an anaesthetic; hence there is no evidence that in 
these experiments the reflex acceleration was not due to a diminution 
of the tonic activity of the vagi. Von Cyon also describes an experi- 
ment in which stimulation of the central end of the superior laryngeal 
caused reflex acceleration; 4 but here also the vagi were intact and in 
tonic activity, as their subsequent section showed. Moreover, the 
increase in the heart rate from stimulating the superior laryngeal 
was far less than that following division of the vagi. 
Careful examination of the accounts of various other experiments 
on this subject shows that in most of the cases in which reflex acceler- 
ation has been described the vagi were intact, and there is frequently" 
1 Roy and Adami : Philosophical transactions, 1892, 183 B, p. 254. 
2 von Cyon : Archiv f. d. ges. Physiol., 1898, lxx, p. 126. 
8 This “ third root ” of the depressor springs from the superior cervical ganglion 
or from the cervical sympathetic. I may mention in this connection that Dr. Har- 
rington and I found a small nerve in a calf lying very near the vagus and ending 
in the superior cervical ganglion ; stimulation of this nerve caused a marked fall of 
blood pressure and a slight slowing of the heart. Thus this nerve corresponded, 
physiologically, to the depressor. 
4 von Cyon : op. cit., p. 149, Table III. Acceleration of the Mammalian Heart. 
431 
evidence to show that they were in a condition of tonic activity. In 
the description of other experiments nothing is said as to whether 
the vagi were intact or not, while in a few the statement is made that 
reflex acceleration occurred after division of the vagi. Almost every 
statement of the latter kind with which I am acquainted is, however, 
open to criticism. Thus in some of the older experiments not only 
was the acceleration very slight, but it was accompanied in many 
instances by changes in the blood pressure sufficiently great to 
account for the changes in the heart rate. 
Reflex acceleration has been described as resulting from stimula- 
tion of the depressor after section of the vagi; Bayliss,1 for example, 
describes such an experiment, and reproduces a tracing showing the 
acceleration. An examination of this tracing shows that the accel- 
eration is very different from that observed when the accelerators are 
stimulated directly, and arouses the suspicion that it is not a case of 
true reflex acceleration at all. When the accelerator nerves are 
stimulated directly, there is a long latent period, and the acceleration 
is developed slowly; after the stimulation ceases the heart returns 
slowly to its previous rate. In this tracing the heart rate remained 
unchanged during the first two or three seconds of stimulation ; then 
it suddenly doubled, and the heart continued at this greater rate 
until after the stimulation had ended, when it suddenly returned to 
its previous rate, i. e. to just one half the accelerated rate. An 
examination of the heart in such cases as the above, in which the 
rate is slowed suddenly to one half the previous rate, usually shows 
that this is due to the failure of the ventricles to follow one half 
of the auricular beats; when, on the contrary, the heart rate is 
suddenly doubled, the ventricles are found to be responding to all 
of the auricular beats. In many animals this lack of co-ordination 
in the beats of the auricles and ventricles is made to disappear by 
influences causing slight changes in the blood pressure or respiration, 
by movements of the animal, by slightly pulling the vagi, etc., and it 
is possible that some such changes as these were the cause of the 
acceleration in Bayliss’s experiment. On the other hand it must be 
remembered that stimulation of the accelerators increases the ease 
with which impulses are conducted from auricle to ventricle, and it 
is possible that in the above experiment the doubling of the heart 
rate was after all due to a reflex stimulation of the accelerators acting 
in this manner; still, I know of no experiments in which direct stim- 
1 Bayliss : Journal of physiology, 1893, xiv, p. 313. 432 
Reid Hunt. 
illation of the accelerators produced this effect without at the same 
time causing an increase in the rate of the entire heart. 
An experiment by Barbera very7 similar to the one described by 
Bayliss is brought forward by v. Cy7on1 as evidence that reflex 
acceleration may under some circumstances be produced by stimula- 
tion of the central end of the cervical sympathetic. In this experi- 
ment, in which the vagi had been cut, the injection of a solution of 
sodium phosphate had caused a decrease of the heart rate to one 
half the previous rate; stimulation of the cervical sympathetic, as 
is shown by the curve published, caused the heart rate to increase 
from 10 to 20 beats in 5 seconds; 2 the latter was practically the rate 
at which the heart was beating before the injection of sodium 
phosphate. Apparently the heart continued to beat at this rate for 
some time after the stimulation ended. Evidently this experiment is 
open to the same criticism as the one discussed above, and it hardly 
can be regarded as a satisfactory7 case of true reflex acceleration. 
Barbera3 describes the effect of stimulating the depressor after 
section of the vagi in the experiment cited by Cyon, just men- 
tioned. He does not publish the curve, or give many details of the 
stimulation, but merely states that the heart rate increased as a result 
of stimulating the depressor from 240 to about 270 beats per minute, 
while the blood pressure fell from 103 to 86 mm. This may be a 
case of true reflex acceleration; but it may fairly be asked if in an 
animal in which, apparently as a result of repeated injections of 
sodium phosphate, the heart rate was as easily affected, as numerous 
statements show it to have been in this one, the fall of blood pressure 
may not have been the cause of this acceleration of the heart. I 
may add, moreover, that I know of no experiment in which the 
evidence for the occurrence of reflex acceleration after section of 
the vagi is stronger than in this one. 
Attention was called above to the fact that very few of the authors 
who speak of reflex acceleration take into consideration the possi- 
bility of its being caused by diminution of the tonus of the vagi; in 
fact I know of but one paper (by MacWilliam) dealing directly with 
1 von Cyon : op. cit., pp. 202-203. 
2 It may be that in some of these cases the doubling of the rate of the ventricle 
was only apparent, one strong beat being followed by a weaker beat; the result 
being that the two beats were recorded by the mercury manometer as one. How- 
ever these changes are produced, they are evidently not satisfactory evidence of a 
reflex stimulation of the accelerators. 
3 Barbara: Archiv f. d. ges. Physiol., 1897, Ixviii, p. 444. Acceleration of the Mammalian Heart. 
433 
this subject. Before speaking of MacYVilliam’s work a few words 
may be said about some experiments of other physiologists bearing 
upon this question. 
Schmiedeberg,1 in his classical paper on the accelerator nerves of 
the dog, describes two experiments in which reflex acceleration was 
obtained by stimulating the central end of one of the limbs of the 
annulus of Vieussens. Schmiedeberg does not state whether the 
vagi were cut or not, but I infer that they were not, and from 
the fact that the heart rate increased later in the experiment I infer 
that they were in a condition of tonic activity. Schmiedeberg calls 
attention to the fact that in one of these two experiments the course 
of the acceleration was different from that resulting from direct 
stimulation of the accelerators, in that the after-effect was very short, 
and he expresses a doubt as to whether the acceleration was due to a 
reflex stimulation of the accelerator nerves ; he does not suggest, how- 
ever, that it may have been due to a diminution of the vagus tonicity. 
Asp 2 made a number of experiments on the effect upon the heart 
rate of stimulating sensory nerves both before and after section of the 
vagi; he also made four experiments in which the accelerators were 
cut. Asp observed slight acceleration upon stimulating sensory 
nerves after the vagi were cut; the effect upon the blood pressure 
was variable. In two of the four experiments in which the acceler- 
ator nerves had been cut slight reflex acceleration occurred; in the 
two other it did not occur, although it had been obtained in all four 
experiments before the accelerators were cut. Asp was endeavoring 
to determine whether reflex acceleration is due to a stimulation of 
the accelerator nerves or, as he puts it, to “ a constriction of the 
arteries of the brain, caused by a stimulation of the sensory nerve, 
by which the pressure on the vagus centres was reduced and the 
heart became more rapid.” Neither Asp nor Schmiedeberg seems 
to have considered the possibility of the reflex inhibition of the 
cardio-inhibitory centre. 
These experiments of Asp are sometimes cited as evidence of 
reflex stimulation of the accelerator nerves, and Asp himself was 
inclined to interpret them in this manner, although he states dis- 
tinctly that he did not consider the question closed. The reflex 
acceleration was not marked ; blood pressure changes could not be 
1 Schmiedeberg : Sitz.-Ber. d. sachs. Gesell. d. Wiss., math.-phys. CL, 1871, 
p. 152. 
2 Asp: Sitz.-Ber. d. sachs. Gesell. d. Wiss., math.-phys. CL, 1867, p. 188. 434 
Reid Hunt. 
excluded, and finally, as Asp points out, the heart was irregular and 
the effect of stimulating sensory nerves very uncertain. 
Knoll1 found that compression of the heart, either by the finger 
or by inflating the pericardium with air, caused an acceleration of 
the heart, and he showed that this acceleration was due to a diminu- 
tion of the tonicity of the vagi. 
MacWilliam 2 is apparently the only author who has given careful 
attention to the question as to the manner in which reflex accelera- 
tion is brought about when an ordinary sensory nerve is stimulated, 
but he has published only a preliminary paper containing few details. 
MacWilliam compared the latent period of direct and of reflex 
acceleration, and reached the conclusion that the latent period of the 
latter is too short for the acceleration to be referred to a stimulation 
of the accelerator nerves; he thinks it is due to a diminution of the 
tonus of the vagi. The effect upon the heart rate of stimulating the 
sensory nerves before and after section of the vagi, and of stimulating 
the accelerators, was also studied by MacWilliam, with the result 
that reflex acceleration was obtained after the accelerators were cut 
if the vagi were intact, but not after the vagi were cut, although the 
accelerators were intact. From these experiments MacWilliam drew 
the conclusion that, ordinarily, reflex acceleration is due to a diminu- 
tion of the tonus of the vagi. 
The afferent nerves by which reflex acceleration is produced. — 
The nature of the afferent nerve fibres by which reflex acceleration 
and reflex slowing of the heart are produced has received but little 
attention. Tigerstedt,3 after discussing the various experiments on 
this subject, states what may perhaps be regarded as the current 
view of physiologists, namely, that both the accelerator and inhibitory 
nerves can be thrown into reflex activity by the stimulation of almost 
all afferent nerves. 
There is evidence, however, that the various sensory nerves differ in 
their effect upon the heart; some for example cause as a rule reflex 
acceleration, others, reflex slowing. To the latter class, as Tiger- 
stedt pointed out, belongs the trigeminus; stimulation of this nerve 
1 Knoll: Lotos, neue Folge, 1881, ii, p. 14. 
2 MacWilliam: Proceedings of the royal society, London, 1893, liii, p. 464. 
It is but fair to myself to state that most of my experiments were performed before 
I learned of MacWilliam’s paper; in fact, the greater part of this section of my 
paper was written a number of years ago, and originally included in a thesis pre- 
sented to the Johns Hopkins University for the degree of doctor of philosophy. 
J Tigerstedt : Lehrbuch der Physiologie des Kreislaufes, 1893, p. 289. Acceleration of the Mammalian Heart. 
435 
seems always to cause reflex slowing, if it has any effect at all upon 
the heart. Asp 1 states that, as a rule, he observed acceleration to 
follow stimulation of the central end of muscular branches of nerves; 
but in some experiments reflex slowing occurred. Tengwell,2 how- 
ever, found the stimulation of muscular nerves had but little effect 
upon the heart rate. Roy and Adami3 found reflex acceleration 
usually resulted from stimulation of the sciatic nerve; sometimes the 
acceleration was followed by a slowing of the heart. The latter 
nearly always occurred when the splanchnic nerve was stimulated. 
Schmiedeberg 4 observed in two of his experiments that stimulation 
of the central end of one limb of the annulus of Vieussens caused 
reflex acceleration, whereas stimulation of the other limb caused reflex 
slowing; he suggests that there are several varieties of afferent nerve 
fibres, some of which cause reflex acceleration and some reflex slowing. 
Statements and speculations as to the nature of the afferent nerve 
fibres concerned in reflex acceleration, however, have only a second- 
ary interest, so long as the question of the manner in which this 
acceleration is caused is left undecided; for if it should be shown 
that reflex acceleration is in reality due to an inhibition of the cardio- 
inhibitory centre, the effect of stimulating various nerves might be 
determined solely by' the condition of this centre at the time of 
stimulation. 
On the Manner in which Reflex Acceleration is produced. 
The problem whether the reflex acceleration resulting from the 
stimulation of sensory nerves is caused by a diminution of the to- 
nicity of the vagi, or by an increased action of the accelerators, was 
approached from three standpoints: (1) the details of some of the 
1 Asp: op. cit., p. 183. The statement of Asp that mechanical stimulation of 
the sciatic plexus causes a reflex slowing of the heart, whereas electrical stimula- 
tion causes an acceleration, is often quoted. I can find but one experiment of this 
kind described in Asp’s paper (p. 182), and this is most unsatisfactory on account 
of the great differences produced in the blood pressure in the two cases; with 
mechanical stimulation the blood pressure rose 106 mm., while with electrical 
stimulation there was a rise of but 37 mm. Some of Asp’s experiments upon the 
effect of stimulating the lumbar cord are open to a similar criticism ; thus he com- 
pares the effects of two stimuli (one mechanical and the other electrical) upon the 
heart rate, although in the one case the blood pressure rose to 100 mm. and in the 
other to 174 mm. Some of these experiments will be referred to again. 
2 Tengwell : Skandinavisches Archiv f. Physiol., 1895, vi, p. 230. 
3 Roy and Adami : Philosophical transactions, 1892, 183 B, p. 258. 
4 Schmiedeberg: Ber. d. sachs. Gesell. d. Wiss., math.-phys. Cl., 1870, p. 152. 436 
Reid Hunt. 
events occurring in the heart when it was thrown into a condition of ac- 
celeration in various ways were investigated, (2) the accelerators were 
cut and sensory nerves stimulated, and (3) the vagi were divided and 
sensory nerves stimulated. 
The duration of systole and diastole and the latent period when the 
heart rate is increased in various ways. — The duration of systole and 
diastole, and the latent period of acceleration, were determined when 
the heart rate was increased by the stimulation of a sensory nerve, 
and these results were compared with those obtained by cutting the 
vagi and by stimulating the accelerators directly. If the acceleration 
occurring in the former case is due to a diminution of the tonic 
activity of the vagi, we should expect to find the course of the 
acceleration similar to that resulting from section of the vagi, rather 
than to that observed when the accelerators are stimulated directly; 
the former is, as a rule, the case, as the following experiments show. 
The duration of systole and diastole, and of the latent period, was 
determined by means of Hurthle’s manometer, in the manner described 
in the first part of this paper. At times the dicrotic wave on the 
curve of carotid pressure became so indistinct that it was impossible 
to determine accurately the duration of systole; such tracings could 
be used, however, for determining the latent period. 
The results obtained from the various experiments were so uniform 
that only one or two experiments of each class need be described. 
Section of the vagi.—The following experiment shows the usual 
effect upon the heart-beat of cutting the vagi when these are in a 
condition of tonic activity". 
Experiment A. Very small dog. Morphine and ether. Left carotid con 
nected with Hurthle’s manometer. Left vagus had been cut. 
Time. Duration in seconds of 
Hrs. min. Systole. 
Diastole. 
3 50 0175 
0.495 
0.165 
0 495 
R. vagus cut. 0.175 
0.365+ 
0.165 
0.365+ 
0.170- 
0.330 
0.165 
i 
0.305 
0.280+ 
0.165- 
— 
Time. 
Duration in seconds of 
Hrs. min. sec. 
Systole. 
Diastole. 
0.165- 
— 
3 50 
— 
— 
0.155+ 
0.260 
— 
0.260 
0.150 - 
— 
0.145 
— 
10 
0.140 
0 255 
12 
0130+ 
0.255 
1+ 
0.120 
0.255 
1 In this and subsequent tables the dash (—) means that the curves were not 
counted out in full; the labor of counting these tracings to hundredths of seconds 
is very great. Acceleration of the Mammalian Heart. 
437 
These results are shown in the plotted curve of Fig. 6 better than 
in the table; the ordinates represent the duration of systole and 
diastole in 0.C5 
of a second, the 
abscissae five 
heart - beats. In 
Fig. 7 a small part 
of the original 
tracing is repro- 
duced. 
The chief ef- 
fects upon the 
heart rate of cut- 
ting the vagi, as 
shown by the 
above experi- 
ment, are (1) the 
very sudden and 
great decrease in 
the duration of 
diastole, and (2) 
the much more slowly developed and relatively 
less marked effect upon the systole. The short- 
ening of diastole began in the heart-beat during 
which the vagus was cut, and had reached 
almost the maximum before the shortening of 
systole began. These results are in accord with 
the well-known fact that it is the diastole which 
is most easily and quickly affected when the 
heart rate is altered, and that the influence of 
the vagus upon diastole is greater than its in- 
fluence upon the systole. 
Results very similar to the above are ob- 
tained when the heart returns to its normal 
rate after it has been slowed by stimulation of 
the peripheral end of the vagus or when it has 
been slowed reflexly. 
Stimulation of the accelerators.—An experi- 
ment was described in the first part of this paper (p. 402) showing 
the effect upon the duration of the systole and diastole of cutting 
Figure 7. Two thirds the original size. Experiment A. Part of record taken with Hurthle’s manometer to show effect 
of cutting the right vagus. Time in intervals of 0.01 and 1 second intervals. To be read from left to right. 
Figure 6. Experiment A. Section 
of right vagus. The ordinates 
represent the duration of systole, 
S, and of diastole, D, in 0.05 
seconds; the abscissae, 5 heart- 
beats. 43$ 
Reid Hunt. 
the accelerator nerves; the following table and curve (Fig. 8) show 
the effect of stimulating the accelerators in this experiment. 
Time. Duration of 
Heart-beats 
Hrs. min. Systole. 
Diastole. 
in io seconds. 
2 3 0.285 
0.310 
16| 
0.300+ 
0.325 
R. ann. stim. ; coil 10 cm. 
0.285 
0.305 
0.265 
0.330 
0.300 
0.330 
0.280 
0.305 
21! 
0.265 
0.265 
0.240+ 
0.275 
0.235 
0.260 
0.215+ 
0.245 
0 230 
0.240- 
0.195 
0.225 
0.180 
0.220+ 
0.175 
0.210+ 
0.160 
0.215+ 
0.155 
0.200 
Stim. off annulus. 
0.160 
0.190+ 
(Every 5th beat counted.) 
0.145+ 
0.205 
28+ 
0.140+ 
0.210+ 
0.145+ 
0.205+ 
0.140 
0.220 
The exception- 
ally long duration 
of the systole in 
this experiment 
was caused by the 
section of the ac- 
celerators. 
This experiment 
shows that stimula- 
tion of the accelera- 
tors causes a short- 
ening of systole as 
well as of diastole, and that the latent period of each is very long; 
in fact, the maximum shortening occurred after the cessation of 
the stimulation. 
Figure8. Experiment C. Stimulation of the right annulus 
(x to x). The ordinates represent the duration of systole, 
S, and of diastole, D, in 0.05 seconds; the abscissae, 5 
heart-beats. Acceleration of the Mammalian Heart. 
439 
Curves very similar to the above are obtained when the accele- 
rators are stimulated during a long stimulation of the vagi, by which 
the heart is slowed. Occasionally, however, when the heart rate 
is very slow, either in conse- 
quence of the stimulation of 
the vagi,1 or of the tonic activ- 
ity of these nerves, or from 
other causes, and the stimulus 
applied to the accelerators is 
very strong, the latent period 
is much shorter than in the 
above experiment,2 and the 
diastole is much shortened be- 
fore the shortening of the sys- 
tole begins. In such cases the 
curve is intermediate in form 
between those resulting from 
section of the vagi and those 
usually following stimulation 
of the accelerators. 
Acceleration of the heart resulting from stimulation of a sensory 
nerve. — The following experiment illustrates the effect upon the 
heart rate of stimulating a sensory nerve. 
Experiment E. Medium-sized dog. Morphine and ether; curare. The 
following table and curves (Figs. 9 and 10) show the effect upon the heart of 
stimulating the saphenous nerve. 
Figure 9. Experiment E. Stimulation of 
saphenous. (See above table.) The ordi- 
nates represent the duration of diastole, D, 
and of systole, S, in 0.05 seconds; the ab- 
scissae represent 5 heart-beats. 
1 Frangois-Franck (Travaux du laboratoire de Marey, 1878-79, p. 80) states 
that the latent period is prolonged when the heart is under the influence of the 
vagus; I have found just the opposite to be the case. There is, moreover, the 
following difference : when the vagi have been divided, or when they are not in 
tonic activity, the latent period of the accelerators is found to be long in both 
systole and diastole, and the shortening of one does not begin before that of the 
other. If, however, the vagi are in activity, stimulation of the accelerators may 
cause a marked shortening of diastole before the duration of systole is at all 
affected. When, on the other hand, the vagus is stimulated, the diastole is always 
prolonged before the systole, i. e. the latent period of stimulation of the vagus 
applies especially to the systole. 
2 Hurthle (Archiv f. d. ges. Physiol., 1891, xlix, p. 89) describes an experiment 
on a very slowly beating heart in which the second diastole was shortened ; I 
never have observed a shortening of any diastole before the fourth as a result of 
stimulating the vagus. 440 
Reid Hunt. 
Time. Duration in seconds of 
Hrs. min. Systole. 
Diastole. 
11 23 0.175 
0.415 
0.175 
0.420 
R. saphenous stimu- 
lated for 10 secs.; 
coil 11 cm. 
0.180- 
0.350 
— 
— 
0.165 
0.300 
— 
— 
0.160 
0.290 
— 
— 
— 
— 
— 
— 
0.155+ 
0.280 
— 
— 
— 
— 
— 
— 
— 
— 
0.150 
0.275 
Time. 
Duration in seconds of 
Hrs. min. 
Systole. 
Diastole. 
— 
— 
— 
— 
— 
— 
0.145 
0.265 
— 
— 
— 
— 
— 
— 
— 
— 
0.140 
0.255 
Stimulus 
off saphe- 
nous. 
0.140+ 
0.270+ 
— 
— 
0.145+ 
0.290+ 
— 
0.330+ 
0.150+ 
— 
0.160 
0 430+ 
— 
— 
— 
— 
0.165 
0.505+ 
Examination of the above table and curves shows that the short- 
ening of the diastole is very marked and the latent period very 
short; the effect upon the systole is less marked and is more 
slowly developed. The heart rate also returned very quickly to 
the normal. 
When the effects upon the heart rate of stimulating a sensory nerve 
are compared with those described above, resulting from cutting the 
vagi and from stimulating the accelerators, it is very evident that 
they resemble the former much more closely than they do the latter. 
When the heart is accelerated by section of the vagi, or by the stimu- 
lation of a sensory nerve, the diastole is shortened relatively much 
more than the systole, and the latent period is very short. When, 
however, the accelerators are stimulated directly, the systole as well 
as the diastole is much shortened, and the latent period is very long. 
Moreover, the after-effect upon the heart rate of stimulating the 
accelerators directly is often very different from that occurring in 
reflex acceleration; in the former case the heart continues beating 
at a rapid rate for some time, whereas in the latter it often returns 
very quickly to its previous rate or is slowed. Acceleration of the Mammalian Heart, 
44i 
As the results described above are by no 
means exceptional, but are the rule, I think 
they can be regarded as strong evidence for 
the view that in reflex acceleration of the 
heart diminution of the tonic activity of the 
vagi plays the chief role. 
These results are of a special interest, since 
they suggest that under certain circumstances 
the cause of any sudden increase in the 
heart rate, i. e. as to whether the increase 
is due to stimulation of the accelerators or 
to a diminution of the tonic activity of the 
vagi, can be determined from the cardiogram 
of the intact animal or of man. 
While in most cases the curves of direct 
and of reflex acceleration differ in the man- 
ner described above, there are exceptional 
cases in which the difference is not well 
marked. In some cases of reflex accelera- 
tion, for example, the latent period is com- 
paratively long; this occurs most frequently 
when the heart rate is already rapid and 
the acceleration relatively small. On the 
other hand, the latent period when the ac- 
celerators are stimulated may be very short; 
as already described, this occurs when the 
heart is beating very slowly. Further, the 
difference mentioned above in the effect 
upon systole and diastole, in the two cases, 
is not always marked. Even in these ex- 
ceptional cases, however, the subsequent 
course of acceleration usually differs; the 
maximum shortening is reached much more 
quickly in reflex than in direct acceleration. 
Reflex acceleration after section of the ac- 
celerators. — Such an experiment as the fol- 
lowing shows that marked reflex acceleration 
of the heart may occur after the principal 
nerves containing accelerator fibres have been 
divided. 
Figure io. One half the original size. Experiment E. Part of record taken with the Hurthle manometer to show effect of stimulating 
saphenous nerve; secondary coil 7 cm. Time in 0.01 and 1.0 second intervals. To be read from left to right. 442 
Reid Hunt. 
Experiment 139. Small dog. Morphine and ether. Stellate ganglia and 
their branches exposed. Blood pressure from left femoral artery. 
Time. 
Heart-beats 
Hrs. min. in io 
seconds. 
1 8 
R. saphenous stim. for 10 
14- 
sec.; coil 10 cm. 
22- 
134 
12+ 
HH 
( 1 30 
< to 
Accel, nerves cut. 
( 1 34 
1 39 
R. saphenous stim. for 10 
14| 
sec.; coil 10 cm. 
19! 
Hi 
10 
Time. Heart-beats 
Hrs. min. in io seconds 
104 
40J 
104 
R. saphenous stim. for 10 
sec.; coil 14. 
00 
104- 
10 
94+ 
104 
51 
li 
R. saphenous stim. for 10 
sec.; coil 16 cm. 
17+ 
H4 
104 
Section of the vagi caused the heart rate to increase to 26 beats in 10 
seconds. 
The accompanying curve (Fig. 11) shows the effect upon the heart 
rate of one stimulation of the saphenous nerve in the above experi- 
Figure ii. Two fifths the original size. Experiment 139. Acceleration of the heart 
resulting from stimulation of the saphenous nerve, S-S, after section of the accelera- 
tor nerves. Time in intervals of 10 seconds. Tracing to be read from left to right. 
ment after the accelerators were cut. A glance at this curve shows 
it to be very different from those obtained when the accelerators are 
stimulated directly; in the latter case the latent period is much 
longer, the maximum acceleration is much more slowly reached, 
and the heart rate returns much more slowly to its previous rate. 
The reflex acceleration in this experiment was slightly greater before 
than after the accelerators were cut; this feature, which frequently Acceleration of the Mammalian Heart. 
443 
occurs, will be discussed below, but it evidently does not interfere 
in the least with the conclusion that in reflex acceleration diminu- 
tion of the tonicity of the vagi plays the chief role. 
Results similar to the above were secured in a large number of 
experiments. In fact whenever reflex acceleration was obtained 
with the accelerators intact, it was obtained also after these nerves 
had been divided, provided the tonicity of the vagus centre was not 
destroyed by the operation. The operation necessary to expose the 
accelerators and the section of these nerves tend to reduce or to 
abolish permanently the vagus tonicity; if this occurs, no reflex 
acceleration takes place.1 In order to get the best results it is well 
to proceed as in the above experiment; the stellate ganglia should 
be exposed with as little operating as possible, and then some time 
allowed for the animal to recover. The temperature is prevented 
from falling by keeping the animal on a zinc box filled with warm 
water, and the wounds are carefully covered with towels wet with 
warm saline solution. Finally the nerves are cut with a pair of very 
sharp scissors, and pulling or crushing of the nerves carefully avoided. 
All cases in which reflex acceleration occurred before but not after 
section of the accelerators could be explained by the loss of vagus 
tonicity resulting from the operation. On the other hand, I had 
never observed reflex acceleration to occur except when there was 
clear evidence that the vagi were in tonic activity.2 
Another point of interest in this connection (and the one which 
first led me to suspect that reflex acceleration is due to a diminution 
of the vagus tonicity) is that the rate reached by the heart during 
reflex acceleration is never greater than that following the section 
of the vagi; it may reach this rate, but never exceeds it. 
Certain objections may be raised to the conclusion that in such 
experiments as the above the acceleration was due to a reflex 
diminution of the tonic activity of the vagi. Thus the acceleration 
might be attributed to the rise of blood pressure which so often 
occurs at the same time. It is not at all uncommon, especially when 
1 It is not improbable that the absence of reflex acceleration in the two experi- 
ments of Asp referred to above (p. 433), in which the stellate and inferior cervical 
ganglia had been removed, was due to the loss of tonicity of the vagi resulting 
from the operation. 
2 Reflex acceleration also occurs in animals in which subsequent section and 
stimulation of the accelerator nerves show them to have been in a condition of 
maximum acceleration ; the reflex acceleration in such cases is obviously due to an 
inhibition of the vagus centre. 444 
Reid Hunt. 
the heart is beating very slowly, for stimulation of a sensory nerve 
to cause a rise of blood pressure and a considerable acceleration of 
the heart even after all the cardiac nerves are divided ; 1 the same 
result may follow stimulation of the peripheral end of the splanchnic, 
both when the cardiac nerves are intact and when they have been 
divided. The course of the acceleration occurring in such cases as 
these, however, is very different from that which occurs when a sen- 
sory nerve is stimulated and the vagi are intact. In the latter case 
the acceleration begins with considerable suddenness; the second 
or third beat may be shortened and a very distinct acceleration 
occur before the blood pressure has begun to rise; in the former 
case the acceleration begins very slowly; I have never observed it 
to begin until after the nerve had been stimulated for at least io 
seconds, and the blood pressure had risen very considerably. 
Moreover, reflex acceleration frequently takes place when the 
change in the blood pressure is insignificant. 
Another possible cause of the acceleration occurring after the 
stellate ganglia and their branches have been extirpated remains to 
be considered, viz. a reflex stimulation of accelerator fibres which 
pass to the heart in the vagus or vago-sympathetic trunk. As is 
well known, the slowing of the heart caused by stimulation of the 
peripheral end of the vagus or of the vago-sympathetic in the dog is 
sometimes followed by an acceleration; if atropine has been given, 
acceleration alone may result. This acceleration at present is usually 
explained by supposing that there are certain accelerator fibres which 
reach the heart by this route, and the possibility of reflex accel- 
eration being produced by means of such fibres must be considered. 
Certain considerations, however, make it very improbable that these 
fibres play any important part in the production of reflex accelera- 
tion. In the first place, it is rather exceptional to find any evidence 
for the existence of accelerator fibres in the vago-sympathetic of the 
dog; reflex acceleration is very frequently obtained after removal of 
the stellate ganglia in animals in which no acceleration is observed 
when the vago-sympathetics are stimulated either before or after the 
administration of atropine. When stimulation of the vagus does 
cause acceleration after atropine, the curve closely resembles that 
observed when the other accelerators are stimulated, and is not at 
1 The acceleration observed in such cases may not be due to the rise of blood 
pressure, but to the warm blood which is forced suddenly into the heart from the 
abdominal viscera. Cf. Martin: Physiological papers, 1895, p. 18. Acceleration of the Mammalian Heart. 
445 
all like that obtained in reflex acceleration. Moreover, the accelera- 
tion caused by the direct stimulation of these nerves is seldom so 
great as that which is often obtained reflexly by the stimulation of 
sensory nerves. 
Stimulation of sensory nerves after section of the vagi. — The ques- 
tion, Does reflect acceleration occur after section of the vagi? may 
now be discussed. It may be said at once that in a large number of 
experiments stimulation of sensory nerves caused either no accelera- 
tion at all after section of the vagi, or the acceleration was so slight 
that it could be referred probably to changes in blood pressure; in 
no case was there evidence that the slight acceleration was due to 
stimulation of the accelerator nerves, for such changes in the heart 
rate occurred after these nerves as well as the vagi had been cut. 
No reflex acceleration took place after the vagi had been cut in cases 
in which all the conditions seemed very favorable, i. e. in cases in 
which marked reflex acceleration had been observed before the vagi 
were cut, and in which, as subsequent examination showed, the 
accelerators were not in a condition of maximum activity and were 
very irritable. 
The question may be raised, if after the vagi were cut the heart was 
not already beating at so rapid a rate that the conditions were not 
favorable for the occurrence of reflex acceleration, although the 
accelerator centres may have been irritable. This rapid rate of the 
heart, however, could not account for the entire absence of reflex 
acceleration, for the maximum rate to which the heart can be ac- 
celerated is independent of the rate at which the heart beats before 
stimulation,1 and it is very rare for the heart to be in a condition of 
maximum acceleration after section of the vagi. Still, if the heart 
was beating slowly before reflex acceleration occurred, the relative 
increase would be greater, and hence more striking. Accordingly, in 
a number of experiments in which the heart rate had increased as a 
resuit of cutting the vagi, the peripheral end of one or of both of 
these nerves was stimulated with a current just sufficient to bring the 
heart back to the rate at which it was beating before the nerves were 
cut. Stimulation of sensory nerves in such cases never caused any 
acceleration, although direct stimulation of the accelerators caused a 
great increase in the rate. 
These experiments are of interest in connection with the work of 
Roy and Adami. These authors agree with me as to the absence of 
1 Bowditch : Ber. d. sachs. Gesell. d. Wiss., math.-naturw. Cl., 1871, p. 266. 446 
Reid Hunt. 
reflex acceleration after section of the vagi,1 but give an entirely 
different explanation. Roy and Adami explain reflex (and also 
direct) acceleration of the heart as due to a diminution of the vagus 
tonus in the heart resulting from the action of the accelerator nerves; 
after section of the vagi, reflex or direct acceleration of the heart is 
impossible, since there is no vagus tonus in the heart to overcome. 
If this explanation were correct, it is impossible to see why reflex 
acceleration does not occur when the effect of the vagi upon the 
heart has been restored by the artificial stimulation of these nerves. 
A few experiments on the effect upon the heart rate of stimulating 
the cerebral cortex may be referred to here. The suggestion that 
the accelerator nerves may be thrown into activity by processes 
originating in the cerebrum is frequently made; hence it seemed 
possible that stimulation of the cerebral cortex might yield interest- 
ing results. Accordingly in a number of experiments upon dogs the 
motor areas and various parts of the frontal and occipital lobes were 
stimulated with the faradic current. Acceleration of the heart 
frequently occurred when the vagi were intact and in tonic activity, 
but no acceleration was obtained after section of the vagi, either when 
the heart was beating rapidly, or when it was slowed by stimulating 
the peripheral end of the vagus. 
Influence of the tonic activity of the accelerators upon reflex accelera- 
tion.— Although, as has been shown above, reflex acceleration is due 
to a diminution of the tonus of the vagi, and occurs after the acceler- 
ator nerves have been divided, yet these nerves, if they are in a 
condition of tonic activity, exert a modifying influence upon the 
course of the acceleration. The extent of the reflex acceleration, 
like the increase in the heart rate following section of the vagi, is in 
fact determined by two factors, — the cutting off of the influence of 
the tonic activity of the vagi, which of itself keeps the heart beating 
slowly, and the removal of the check to the tonic activity of the 
accelerators. 
This influence of the tonic activity of the accelerators is shown in 
three ways. In the first place, the rate to which the heart is accel- 
erated is, as a rule, greater when these nerves are intact than when 
they have been divided. Secondly, the course of the acceleration is, 
or may be, somewhat different; there may be, to begin with, a very 
sudden and marked acceleration, due to the inhibition of the tonic 
inhibitory impulses, and then an acceleration more slowly developed, 
1 Roy and Adami : Philosophical transactions, 1892, 183 B, p. 267. Acceleration of the Mammalian Heart. 
447 
due to the accelerator nerves; whereas after section of the acceler- 
ators reflex acceleration usually reaches its maximum very quickly, 
and is often followed by a partial return to the normal while the 
stimulation continues. In the third place, the after-effect of the 
stimulation is often different: when the accelerators are intact, 
the rate may continue rapid for some time after the stimulation 
ceases, and only slowly return to the normal, or give way to a 
secondary slowing. If, however, the accelerators have been divided, 
the rate after stim- 
ulation of a sen- 
sory nerve usually 
returns quickly to 
the normal, or per- 
haps more fre- 
quently is followed 
by a reflex slowing. 
All three of the 
above points are 
illustrated by the 
curves in Fig. 12; 
these results were 
obtained from an 
experiment upon a 
dog. 
Stimulation of 
the saphenous in 
this case, when 
both vagi and accelerators were intact, caused the heart rate to increase 
from 22I to 31+ beats in 10 seconds. Section of the accelerators 
caused the heart rate to decrease to 1 in 10 seconds; stimulation of 
the saphenous now with the same strength of current as above caused 
the heart rate to be increased to but beats in 10 seconds. Of 
course the objection may be made that the more rapid rate in the 
former case (i. e. when the heart rate increased to 31) was due in part 
to a reflex stimulation of the accelerators, and not exclusively to a 
diminution of the tonic activity of the vagi. That, however, the latter 
factor alone is sufficient to account for the acceleration is shown by 
the following fact: before the saphenous nerve was stimulated or the 
accelerators cut, the conductivity of the vagi was suspended by ether 
vapor with the result that the heart rate increased to 34 in 10 seconds. 
Figure 12. Experiment H. Stimulation of the saphenous, 
A, before, B, after, section of the accelerator nerves. The 
stimulation continued 10 seconds in each case ; the 
strength of the stimulating current was also the same. Or- 
dinates represent the duration of the heart-beat in 0.05 
seconds ; the abscissse, 5 heart-beats. 448 
Reid Hunt. 
The rate 31 therefore does not represent the maximum acceleration 
which might have resulted from inhibition of the inhibitory impulses. 
The vagi were afterward cut with the result that the heart rate in- 
creased to 29 beats in 10 seconds. 
To summarize the results of this experiment and to show how 
completely the heart rate is determined at any given time by the 
interaction of the inhibitory and accelerator nerves, the following 
table may be given. 
Vagi and accelerators intact and in tonic activity 
Heart rate in 
io seconds. 
... 22 
Activity of vagi suspended by ether vapor, the accelerators being intact . 34 
Accelerators cut, vagi intact and in tonic activity 
... 19 
After section of accelerators and vagi 
... 29 
Reflex acceleration, accelerators and vagi being intact .... 
... 31 
Reflex acceleration after section of the accelerators 
... 24 
Stimulation of accelerators (weak current), vagi being intact . 
... 27 
Stimulation of accelerators (current as before), vagi cut . . . 
... 34^ 
If, returning to the course of reflex acceleration, we compare the 
two curves given in Fig. 12, the following differences will be observed. 
When the accelerators were intact and the saphenous nerve stimu- 
lated, there was first a sudden marked shortening of the duration of 
the heart-beat; this was followed by a longer period in which the 
heart rate was very slowly increased. After cessation of the stimula- 
tion the acceleration of the heart continued for some little time. 
When, on the other hand, the saphenous was stimulated after section 
of the accelerators, there was also a sudden increase in the heart rate ; 
but this was soon followed by a slight slowing, and immediately after 
the stimulation there was a very marked slowing. 
The curves given above are intended only to illustrate the differ- 
ences which the section of the accelerators may make in a given 
experiment in the course of reflex acceleration ; they are not intended 
to serve as types of the reflex acceleration occurring before and after 
section of the accelerators. No such types can be given, for the 
course of acceleration is seldom the same in any two experiments. 
Thus in one experiment the acceleration may be followed by reflex 
slowing, even during the stimulation of the sensory nerve, although 
the accelerators are intact and in tonic activity; whereas in another 
experiment reflex acceleration may continue long after the cessation 
of the stimulation, although the accelerators have been divided. In 
any one experiment, however, the section of the accelerators usually Acceleration of the Mammalian Heart. 
449 
has some such effect as that described in the above case, i. e. the 
maximum acceleration is less and is more quickly developed and 
there is a greater tendency to a subsequent slowing. 
The parts taken by the inhibitory and accelerator nerves in causing 
reflex changes of the heart rate find a striking analogy in the relation 
of the oculo-motor and sympathetic nerves in reflex movements of 
the pupils. Thus, according to Braunstein,1 reflex dilatation of the 
pupil is due to an inhibition of the tonic activity of the oculo-motor 
centre, for it occurs after section of all the pupil-dilating fibres, if 
the oculo-motors are intact; on the other hand, no reflex dilatation 
of the pupil occurs after section of the oculo-motors although the 
pupil-dilating fibres are intact.2 Moreover, just as the tonic activity 
of the accelerator nerves modifies the course of reflex acceleration 
of the heart, so the tonic activity of the pupil-dilating fibres modifies 
the course of the reflex dilatation of the pupil; after section of these 
fibres the dilatation occurs more slowly, as some of the “ dilating 
force ” is lost. 
Some influences affecting the condition of the cardio-inhibitory centre. 
— With the exception of the respiratory centre there is perhaps no 
medullary centre in the cat and dog so easily influenced as that of 
the inhibitory nerves of the heart; Hering’s experiments on rabbits 
show that this, probably, is true for these animals also.3 
No attempt will here be made to discuss the influences affecting 
the condition of the cardio-inhibitory centre with any degree of 
fulness; only a few factors will be noted which it is necessary to 
take into consideration in connection with the question of reflex 
acceleration. 
Some influences increase, others decrease, the tonic activity of the 
cardio-inhibitory centre; among the former may be mentioned high 
blood pressure and deficient respiration, and among drugs morphine 
and, apparently, small doses of curare. Morphine causes slowing 
of the heart not only by its direct action upon the cardio-inhibitory 
centre, but also through its action upon the respiration. In animals 
1 Braunstein : Zur Lehre von der Innervation der Pupillenbewegung, p. 95; 
Wiesbaden, 1894. 
2 In man, also, no reflex movements of the pupil are obtained after complete 
paralysis of the oculo-motor. 
The dilatation of the pupil resulting from stimulation of the cerebral cortex is 
also due, according to Braunstein (p. 116), to a diminution of the tonus of the 
oculo-motor centre. 
3 Bering, H. E.: Archiv f. d. ges. Physiol., 1895, lx, p. 429. 450 
Reid Hunt. 
anaesthetized by means of cerebral pressure the vagi are usually found 
to be in a condition of marked tonic activity. 
Ether and large doses of curare, and of chloroform, decrease or 
abolish the tonus of the vagus centre completely; 1 operations and 
loss of blood have the same effect, so that unless great care is taken 
in operating, the tonus of the vagi is completely lost. 
Not only does the extent of the tonus of the vagi vary widely in 
different animals of the same species, but the susceptibility of the 
centre to influences which increase or decrease the tonus also varies 
in different individuals. In most dogs, for example, morphine causes 
a very slow heart beat, but in some it has almost no effect upon the 
heart rate, although given in very large doses. 
The tonic activity of the vagi seems to be very slight in young 
animals, and to be very easily abolished in them. 
Influence of the condition of the cardio-inhibitory centre upon cardiac 
reflexes. It is obvious that no inhibition of a centre can occur unless 
the centre is in a condition of activity; but the question arises, Is a 
centre more easily inhibited the greater the activity, or is it more 
easily inhibited when influences are at work which tend, of them- 
selves, to weaken the activity? The results of my experiments upon 
the cardio-inhibitory centre indicate very clearly that the latter is the 
case; this was shown best, perhaps, in experiments on dogs narco- 
tized with morphine. In such animals the cardio-inhibitory centre 
is in a condition of marked activity, and stimulation of a sensory 
nerve often has at first no effect; if, however, some drug which of 
itself tends to destroy the tonus of the centre is given, the stimula- 
tion of a sensory nerve may cause a marked acceleration of the 
heart. 
Among the drugs which reduce the irritability of the cardio- 
inhibitory centre are ether and curare, as was mentioned above; if 
one of these is given to an animal under the influence of morphine, 
there may be an increase of the heart rate of short duration, and then 
the slow rate returns; stimulation of a sensory nerve now, however, 
may easily cause an inhibition of the centre and so an acceleration 
of the heart. Similar results are obtained in animals anaesthe- 
tized by cerebral pressure; in these animals the cardio-inhibitory 
centre is in a condition of strong activity, and stimulation of sensory 
1 An irregular rhythm of the heart, probably due to the inhibitory nerves, is 
frequently made to disappear by the administration of ether or of curare, or by the 
stimulation of a sensory nerve, all of which cause a diminution of the vagus tonus. Acceleration of the Mammalian Heart. 
451 
nerves may have no effect upon the heart or may cause a slowing. 
If, however, ether or curare is given, — although no visible change 
is produced, — stimulation of a sensory nerve usually will cause an 
inhibition of the centre. 
If both vagi are intact and in tonic activity, stimulation of a 
sensory nerve may have no effect upon the heart rate; but if one 
vagus be cut, — although this of itself may cause no increase in the 
heart rate, — stimulation of the same sensory nerve may cause a 
marked acceleration. 
Just the converse of the above holds good for reflex slowing of 
the heart. If the irritability of the cardio-inhibitory centre has been 
much reduced so that the heart is beating very rapidly, stimulation 
of a sensory nerve may have no effect upon it; if, however, the res- 
piration is diminished, or the blood pressure increased in some 
manner, or intravenous injections of warm normal saline solutions 
be made, — influences which tend to stimulate the centre, — then 
stimulation of a sensory nerve may cause a marked slowing of the 
heart. 
Such experiments as those briefly sketched above show that in 
order to obtain either reflex inhibition or reflex excitation of the 
cardio-inhibitory centre it is necessary that this centre be in a con- 
dition of unstable equilibrium; if the centre is in this condition, the 
result of stimulating a sensory nerve is determined in part (but 
only in part, as will be shown later) by the rate at which the 
heart is beating when the nerve is stimulated: if the heart is beating 
slowly, reflex acceleration results ; if it is beating rapidly, reflex slow- 
ing occurs. Thus, in one of many experiments the heart rate was 
24 in 10 seconds, and stimulation of the saphenous nerve caused 
the heart rate to decrease to ij\. A small amount of warm normal 
saline solution was injected into the femoral vein, as a result of 
which the heart rate decreased to 18 in 10 seconds; stimulation of 
the saphenous now caused the rate to increase to 26J beats, but after 
the stimulation it returned to 18. 
Repeated stimulation, or sometimes a single stimulation of a 
sensory nerve, tends to cause permanent (i. e. permanent for the 
individual experiment) changes in the heart rate. Thus, if the heart 
is beating slowly, two or three stimulations of a sensory nerve may 
cause an acceleration of the heart which continues for hours, or as 
long as the experiment continues; simply ligating the sciatic nerve 
has caused a similar effect. If, on the other hand, the heart is beat- Reid Hunt. 
452 
ing rapidly, repeated stimulations may cause the rate to become and 
remain slow. 
These are further illustrations of the already mentioned tendency 
of the heart to reach and remain at a constant rate, whenever its rate 
has been changed. 
The afferent nerve fibres by which reflex acceleration is produced. 
— Attention has already been called to the part which the condition 
of the cardio-inhibitory centre plays in determining whether reflex 
acceleration or reflex slowing of the heart follows stimulation of 
afferent nerves: in this section some facts relating to the afferent 
nerve fibres themselves will be discussed. 
Aside from such nerves as the depressors and vagi, which are 
known to contain nerve fibres having special relations to the vaso- 
motor and respiratory centres, there is evidence that there are 
different kinds of afferent nerve fibres in other nerve trunks. 
In a previous paper, for example, I have collected evidence based 
on experiments of Howell and others and of my own which tends to 
show that in most mixed nerve trunks there are two varieties of 
nerve fibres which may influence the vasomotor centre, one causing 
a reflex rise, the other a reflex fall of blood pressure.1 These results 
suggest the question whether those nerve fibres, stimulation of which 
causes a reflex acceleration of the heart, will, under different circum- 
stances (when, for example, the condition of the cardio-inhibitory 
centre has been altered), cause a reflex slowing, or whether, in fact, 
there are two sets of nerve fibres, stimulation of one of which will 
always cause an acceleration, provided it has any effect at all upon 
the heart rate, while stimulation of the other set will cause a slowing. 
Further, what is the relation of the nerve fibres which cause reflex 
changes in the heart rate to those which cause changes in the blood 
pressure ? 
In the historical review given at the beginning of this part of the 
paper evidence was stated that stimulation of some nerves (e. g. 
the trigeminus) nearly always causes a reflex slowing of the heart, 
whereas stimulation of certain other nerves (e. g. the sciatic) more 
frequently causes an acceleration, or an acceleration first and then a 
slowing. I have observed in my own experiments that when the 
saphenous and the sciatic were stimulated in the same animal the 
former usually caused only an acceleration, while the latter frequently 
caused an acceleration followed by a slowing; moreover, slowing 
1 Hunt: Journal of physiology, 1895, xviii, p. 381. Acceleration of the Mammalian Heart. 
453 
alone occurred more frequently from stimulation of the sciatic than 
of the saphenous. Since this difference of action of the various 
nerves was observed in experiments in which there was no reason 
for supposing that the condition of the cardio-inhibitory centre was 
different in one case from its condition in the other, the most prob- 
able explanation is that there are two varieties of nerve fibres in- 
volved, and that one variety occurs in larger number in some nerves 
than does the other variety. 
The fact also that stimulation of such a nerve as the sciatic has 
or may have a twofold action upon the heart, causing first a reflex 
acceleration and then a slowing,1 suggests that there are two sets of 
fibres involved, and that the action of one set becomes evident before 
that of the other.2 Such a double effect upon the heart is never, or 
only very rarely, observed when certain other nerves, such as the 
depressor or trigeminus, are stimulated. 
Working upon this supposition, many experiments were performed 
in the hope of finding a method by which the conductivity or irrita- 
bility of one set of fibres might be suspended while that of the other 
remained. The methods employed were in general the same as 
those which I employed to separate physiologically those nerve 
fibres which cause a reflex fall of blood pressure from those which 
cause a rise, and consisted essentially in subjecting the nerve trunks 
to influences which altered their conductivity or irritability, and then 
observing the effect upon the heart rate of stimulating them in 
various ways; of course precautions were taken to avoid causing, 
at the same time, changes in the cardio-inhibitory centre. Some of 
the methods employed, although giving evidence of the existence 
of two sets of fibres to the vasomotor centre, gave only negative 
results as to the afferent fibres to the cardio-inhibitory centre; one, 
however, the experiments on the regeneration of nerves, gave posi- 
tive results. 
Effect of stimulating the central end of a recently regenerated nerve. 
— Most of these experiments were performed upon the sciatic nerves 
of cats. One nerve was crushed by drawing a ligature tightly around 
1 If, as is often the case, a rise of blood pressure also occurs from stimulation 
of the sciatic, this may be the cause, in part, of the slowing of the heart; the 
latter often occurs, however, when there is no change in the blood pressure, and 
also when there is a fall of blood pressure. 
2 Cf. Meltzer : Archiv fiir Physiologie, 1892, p. 390 (afferent nerves to the 
respiratory centre) ; also my paper on afferent nerve fibres to the vasomotor centre, 
op. cit., p. 406. 454 
Reid Hunt. 
it, high in the thigh; the wound was closed and the nerve allowed 
to regenerate. After a period of five or six weeks, or after signs of 
motion became apparent for some distance down the leg, the animals 
were anaesthetized (usually by cerebral compression), both sciatics 
exposed and divided, and the central ends stimulated with tetanizing 
currents of varying intensities. Six experiments were performed in 
this manner, and in all of them stimulation of the regenerated nerve 
produced a different effect upon the heart rate from that caused by 
stimulating the normal nerve. Stimulation of the former usually 
caused an acceleration of the heart ; in some cases no effect was 
produced, but in none was there a reflex slowing. Stimulation of 
the normal nerve in these animals caused in all cases a reflex 
slowing. 
One of these experiments was as follows. 
Experiment 32. Cat. Left sciatic crushed 42 days previously. Anaesthesia 
caused by cerebral pressure. Blood pressure 100 mm. of mercury. Stimula- 
tion of the left sciatic about inches below point of injury, with currents of 
varying strength, caused a very slight acceleration of the heart; in one case, 
for example, the rate increased from 27 to 29 in 10 seconds, the blood pressure 
remaining unchanged. Stimulation of the right (normal) nerve caused only 
reflex slowing; during one stimulation, for example, the rate decreased from 
to 20 in 10 seconds, while the blood pressure fell 2 mm. of mercury. 
The results of the above experiment differ from those usually 
observed in that stimulation of the nerves in this case caused no 
change in the blood pressure, whereas stimulation of the normal 
nerve usually causes a rise, and stimulation of the regenerated nerve 
a fall, of blood pressure. The absence of any changes in the blood 
pressure in this experiment makes it improbable that blood pressure 
changes were the cause of the difference in the effect upon the heart 
rate in the other experiments; there is, moreover, other evidence for 
this view. Thus, if an unusually long interval be allowed to elapse 
between the crushing and the stimulation of the nerve, the power of 
a portion of the nerve near the point of injury to cause a reflex fall 
of blood pressure may be lost, while that to cause acceleration 
remains. Thus, in one experiment 48 days were allowed to elapse 
between the operation and the stimulation of the nerves; the result 
was that stimulation of the nerve at a certain distance from the point 
of injury caused a rise of blood pressure, while the heart rate was 
increased from 18 to 24 beats in 9 seconds. Also, on the other Acceleration of the Mammalian ft eart. 
455 
hand, stimulation of the normal nerve may occasionally cause a fall 
of blood pressure, although a reflex slowing of the heart occurs. 
I think the above considerations show sufficiently clearly that the 
changes in the heart rate are independent of the changes in the 
blood pressure. 
The most probable explanation of the result of these experiments 
is that in such mixed nerve trunks as the sciatic, there are two sets 
of afferent nerve fibres to the cardio-inhibitory centre, one of which 
causes inhibition, the other stimulation, of this centre, and that in a 
nerve which has been crushed the former regenerates more rapidly 
than do the latter. Of course it is not necessary to suppose that the 
only function of these nerve fibres is to affect the cardio-inhibitory 
centre; they are probably ordinary sensory nerve fibres which can 
cause other reflexes, only some of them are connected with the vagus 
centre in such a way that their stimulation inhibits, while that of the 
other excites, this centre. What little evidence there is to connect 
either of these varieties of nerve fibres with other varieties (those 
causing changes in the vasomotor centre, for example) will be given 
below. 
Effect upon cardiac reflexes of cooling the afferent nerve. — One of 
the simplest ways of separating physiologically the nerve fibres, 
stimulation of which causes a reflex rise of blood pressure from 
those which cause a fall, is to cool the nerve trunk and then stimulate 
it below the point of cooling; the reflex vaso-constrictors lose their 
conductivity at a higher temperature than do the reflex vaso- 
dilators. My experiments so far have failed to show any difference 
in the action of cold upon the fibres causing a reflex slowing and 
those causing a reflex acceleration of the heart. Cardiac reflexes, 
whether acceleration, slowing, or the two combined, as a rule have 
disappeared at about the temperature (io° C. or less) at which a 
reflex rise of blood pressure was no longer obtained ; when the cool- 
ing was continued below this point stimulation of the nerve caused a 
fall of blood pressure but no effect upon the heart rate. 
Effect of varying the strength and rate of stimulation. — My obser- 
vations upon these points were confined almost exclusively to experi- 
ments upon the sciatic of the dog. When stimulation of this nerve 
causes a reflex acceleration, there is usually a certain strength of 
current, varying in different cases, which gives the maximum acceler- 
ation, that is, causes the greatest number of additional heart beats. If 
the strength of the current is reduced below this optimum degree, the 456 
Reid Hunt. 
maximum acceleration reached during stimulation may not at first be 
decreased, but the acceleration does not continue so long after the 
stimulation ceases; if, however, the strength of the stimulus is still 
further reduced, the maximum acceleration becomes less. When, on 
the other hand, the strength of the current is increased beyond the 
optimum, there may be at first a slight increase in the maximum 
acceleration reached, but this is followed by a greater tendency to 
slowing. This tendency to slowing becomes, as a rule, more and more 
marked as the strength of the current is increased, and sometimes 
stimulation produces only slowing; the latter result, however, is rather 
infrequent. As a rule, if there has been an acceleration with a weak 
stimulus, there is an equally great or greater acceleration with a 
stronger stimulus; the tendency to subsequent slowing is greater in 
the latter case.1 
As regards the strength of current necessary to cause reflex changes 
in the heart rate, as compared with the strength necessary to cause 
other reflex effects, it may be said that, in general, when the vagus is 
in tonic activity and the vasomotor centre is irritable, a stimulus too 
weak to affect the one is also usually without effect upon the other. 
Frequently neither the heart rate nor the blood pressure is influenced 
by a stimulus which causes respiratory and other reflex movements. 
The results of stimulating a sensory nerve with a succession of 
induction shocks slowly repeated do not differ materially from those 
obtained with tetanizing currents; the only difference is that with the 
former method the acceleration or slowing is more slowly developed. 
The above experiments and considerations seem to me to afford 
clear evidence for the view that there are two varieties of afferent 
nerve fibres to the cardio-inhibitory centre, one causing an excitation 
and the other an inhibition of this centre. The mere fact that in the 
same animal stimulation of one nerve may cause a reflex slowing and 
stimulation of another, a reflex acceleration of the heart, when the 
condition of the centre has undergone no change, is difficult to 
explain on any other hypothesis. Moreover, in the regeneration 
method we have a means of showing the presence of two sets of 
nerve fibres in the same nerve; when the nerve is crushed and 
1 Simanowsky is quoted (Jahresbericht der Anatomie und Physiologie, 1881, x, 
p. 62) as having observed that stimulation of the brachial and sciatic plexuses 
with a weak stimulus caused an acceleration, while a strong stimulus caused a 
slowing of the heart. MacWilliam (Proceedings of the royal society London, 
1893, liii, p. 471) obtained similar results. Acceleration of the Mammalian Heart. 
457 
allowed to regenerate, those fibres causing an inhibition of the 
centre regenerate earlier than do those which cause an excitation. 
If the cardio-inhibitory centre underwent changes in irritability in 
the course of the experiment, it would be easy to see how stimula- 
tion of the same nerve fibres might in one case cause inhibition and 
in another excitation, just as the condition of the cerebral cortex or 
of the cardiac muscle is supposed to determine whether stimulation 
shall cause inhibition or augmentation; but in the above experiments 
changes in the centre were excluded. 
We have, further, no evidence that stimulation of the one set of 
fibres can ever under any circumstances cause any change but a 
reflex slowing, or stimulation of the other set anything but a reflex 
acceleration of the heart. 
Although, as was shown above, the condition of the cardio-inhibitory 
centre plays an important part in determining the manner in which 
this centre responds to the stimulation of a mixed nerve, such as the 
sciatic, yet this influence is limited to determining whether the centre 
responds to the impulses reaching it along the one or the other set 
of fibres; in other words, when both sets of fibres are stimulated 
inhibition or increased action will result according as the centre is 
more irritable to the one or the other set of impulses. 
The relation which these fibres to the cardio-inhibitory centre bear 
to other nerve fibres — those to the vasomotor centre, for example — 
is an interesting but very complex problem. The experiments on 
regenerating nerves suggested at first that the fibres which cause a 
reflex fall of blood pressure are identical with those causing a 
reflex acceleration of the heart. The experiments on the effect of 
cold upon the nerves, however, show that the two sets of fibres can- 
not be identified in this manner, for cold causes the fibres which 
produce reflex changes in the heart rate to lose their conductivity 
earlier than those which cause a fall of blood pressure. 
For a similar reason it seems impossible to identify the fibres which 
cause a rise in blood pressure with those which cause a slowing of 
the heart. 
Of course the relative irritability of the cardio-inhibitory and vaso- 
motor centres probably exerts an important influence in this matter, 
and a more thorough investigation may show the following view to 
be incorrect, but at present it is difficult to avoid the conclusion that 
we are dealing with four varieties of nerve fibres: (i) those causing a 
reflex rise of blood pressure, (2) those causing a reflex fall of blood 458 
Reid Hunt. 
pressure, (3) those causing a reflex slowing of the heart, and (4) those 
causing a reflex acceleration of the heart. These four varieties of 
nerve fibres are very unequally distributed in different nerve trunks, 
some being entirely absent from certain of them. Thus there is no 
satisfactory evidence that there are fibres in the depressor which ever 
cause a reflex rise of blood pressure,1 or that the saphenous of the 
cat contains any fibres which can cause a fall;2 as has already been 
pointed out, stimulation of the trigeminus, if it has any effect upon 
the heart, always causes a slowing, and v. Cyon3 found only an 
acceleration to result from stimulation of the third root of the de- 
pressor. The glossopharyngeal usually causes a fall of blood pres- 
sure and a slowing of the heart, the infraorbital 4 a rise of blood 
pressure and a slowing of the heart, while stimulation of the sciatic 
may cause either a rise or a fall of blood pressure and either a slow- 
ing or an acceleration of the heart. 
PART III. 
General Consideration of Results. 
Functions of the accelerator nerves. — In speaking of the functions 
of the accelerator nerves it is necessary to distinguish the effect which 
these nerves have upon the rate from their effect upon the force of 
the heart-beat. It is well known that these two effects have no 
constant relation to each other; in fact they seem almost always 
to occur separately. Thus in very few of my own experiments in 
which acceleration of the rate has been observed has there been 
any evidence that the force of the beats has been increased; a rise 
of blood pressure was exceptional, and when present bore absolutely 
no relation to the increase in the rate. Although the same observa- 
tion has been recorded by almost every one who has worked upon 
this subject, the statement is still frequently made that the increase in 
the heart rate leads to a rise of blood pressure. 
On the other hand, in those experiments in which increase in 
the force of the heart-beat has been found to follow stimulation of 
1 See v. Cyon : Archiv f. d. ges. Physiol., 1898, lxx, p. 229. 
2 Hunt : Journal of physiology, 1895, xviii, p. 386. 
3 v. Cyon : op. cit., p. 142. 
4 Knoll: Sitz.-Ber. d. kais. Akad. d. Wiss., math.-naturw. CL, 1885, xcii, 3, 
p. 449. Acceleratio7i of the Mammalian Heart. 
459 
the accelerators there has been as a rule little or no acceleration of the 
rate. Thus in my own experiments when a rise of blood pressure 
occurred it usually resulted from stimulation of the accelerators of 
the left side, and as I have already shown these nerves have, as a 
rule, but little effect upon the heart rate. It is interesting that in the 
experiments which Roy and Adami,1 who studied the effect of the 
accelerators upon the force of the heart-beat very carefully, quote to 
show the effect of direct stimulation of these nerves upon the heart, 
there is a marked increase in the force of the heart while there is 
scarcely any change in the rate. 
Such facts as the above have led to the suggestion that there are 
really two kinds of nerve fibres in the accelerator nerves: one which 
causes increase in the rate, and another which causes an increase in 
the force of the beat. The former variety may be called the acceler- 
ator, the latter the augmentor nerve fibres. 
The function of the augmentor fibres is doubtless to cause a rise of 
general blood pressure, or, as Roy and Adami2 put it, “ they sacrifice 
the heart in order to increase the output of the organ and enable the 
ventricles to pump out their contents against heightened arterial 
pressure.” 
The principal functions which can be ascribed to the nerve fibres 
which cause an increase in the rate of the heart with no effect upon 
the blood pressure have been referred to already when their tonic 
activity and relation to the vagi were discussed. From the experi- 
ments on the effects of cutting these nerves two conclusions may be 
drawn: (1) the normal rate of the heart is determined in part by the 
impulses constantly reaching it through these nerves, (2) in cases in 
which the irritability of the heart is low, the tonic activity of these 
nerves plays an important part in maintaining the regular rhythm of 
the heart. Attention was also called to the fact that the accelerator 
centres and nerves are very resistant to influences (low blood pres- 
sure, extreme asphyxia, certain drugs, etc.) which quickly depress 
other nerve centres and even affect the cardiac muscle itself; 
hence these nerves, in virtue of their tonic activity, are in a posi- 
1 Roy and Adami : Philosophical transactions, 1892, 183 B, p. 244, see curve 
14, p. 239, stimulation of left annulus, and curve 15, p. 241. In most of the ex- 
periments upon which these authors base their views of the effect of the accel- 
erators upon the force and output of the heart acceleration was produced reflexly 
by the stimulation of a sensory nerve; as has been shown above it is very improb- 
able that the acceleration in such cases was due to the accelerator nerves at all. 
2 Roy and Adami : op. cit., p. 296. 460 
Reid Hunt. 
tion to supply an efficient stimulus to the heart when one is most 
needed. 
It was shown further that the tonic activity of these nerves limits 
the action of the vagi; when the heart is slowed by reflex stimula- 
tion of the vagus, not only do the accelerators limit the extent of 
the slowing, but they enable the heart to return more quickly to its 
normal rate. It is probable that this action of the accelerators is 
very important in counteracting influences which cause reflex slow- 
ing of the heart, such, for example, as injury to the abdominal viscera, 
and perhaps also in asphyxia. 
Nothing definite can be said as to the part the accelerators play 
when they are thrown into increased activity, as so little is known 
about the conditions under which this occurs; in fact, little can be 
added to the statements made by the brothers Cyon more than thirty 
years ago. These physiologists, who recognized that there is not 
necessarily an increase in the work done when these nerves are 
stimulated, suggested that their function consisted in diminishing 
the resistance which the vagi opposed to the development of the 
heart-beat. 
Although the total amount of work done by the heart when it is 
accelerated by stimulation of these nerves is not increased (the work 
being simply differently distributed in time, as the Cyons expressed 
it), yet, as has been already shown, this acceleration causes fatigue of 
the heart; perhaps this fatigue is due to the shortening of the periods 
during which the heart is at rest. In what manner either the heart 
itself, or the rest of the body, benefits by the more rapid rate (which 
of itself causes fatigue of the heart) is obscure. 
Possibly some clue to this problem is to be found in the work on 
the transfusion of blood through isolated organs. It has become the 
generally recognized view that in such experiments much better results 
are obtained when the stream of blood is supplied intermittently 1 
than when it is supplied at a constant pressure. If the blood is sup- 
plied under constant pressure, oedema and other pathological changes 
appear in the organ under experiment,2 and the circulation is soon 
slowed, or even arrested altogether; this is due in part to the cor- 
1 Although Kronecker, in 1871, stated that less injury is done to the vessels of 
a muscle by high pressure if this is intermittent than when it is constant, Stevens 
and Lee (Studies from the biological laboratory, Johns Hopkins University, 1884, 
iii, p. 109) seem to have been the first actually to make use of an intermittent 
supply of nutrient fluid in transfusion experiments. 
2 Hamel: Zeitschrift fur Biologie, 1889, xxv, p. 492. Acceleration of the Mammalian Heart. 
461 
puscles adhering to the walls of the blood vessels and to each other,1 
and even a great increase in the pressure causes but a temporary 
improvement. If, however, the blood is supplied intermittently, the 
slight movement of the corpuscles at each pulsation and the conse- 
quent changes in the diameter of the blood vessels prevent this 
clumping together of the corpuscles, and the transfusion can be con- 
tinued for a much longer time at a comparatively low pressure.2 
I have been unable to find any statements as to the number of 
pulsations per minute which yield the best results in transfusion ex- 
periments; this number would probably be influenced by such 
factors as the nature of the blood-vessel walls, the length of the 
capillaries, etc., so that it is very probable that a rate which is 
suitable for one organ would not be adapted to another. Support 
for this supposition is found in v. Cyon’s work on the circulation 
through the thyroid gland : 3 v. Cyon showed that when the heart 
was beating slowly, as a result of stimulating the vagus, a much 
greater amount of blood flowed from the thyroid vein than when the 
heart was beating more rapidly, although the blood pressure was the 
same and vasomotor changes in the gland were excluded ; the outflow 
from the saphenous vein was also increased, but relatively to a much 
less degree than that from the thyroid vein. 
In the light of such, experiments as the above it seems quite proba- 
ble that conditions may arise under which the circulation of an organ 
may be better provided for by’ a series of rapid heart-beats, each of 
which throws out a smaller quantity of blood, than by a slower rate 
with which the output at each beat is greater. In fact certain 
changes in the respiratory waves of the curve of blood pressure result- 
ing from the stimulation of the accelerator nerves seems to point to 
such an action. One of the most constant effects upon the blood pres- 
sure curve of stimulating the accelerator nerves is a marked increase 
in the amplitude of the undulations; this occurs not only 
when the blood pressure rises or remains at the same level, but also 
when it falls; and further, it occurs in animals under curare and in 
which artificial respiration is maintained by a pump or pair of 
bellows which discharges with great regularity’ the same amount of 
1 von Frey: Archiv fur Physiologie, 1885, p. 538. Welch and Mall consider 
that the absence of pulsation in an occluded artery plays an important part in the 
production of a haemorrhagic infarction. 
2 Jacobi: Archiv f. exper. Pathol, u. Pharmakol., 1890, xxvi, p. 398. 
3 v. Cyon: op. cit., p. 161. 462 
Reid Hunt. 
air at each stroke. If changes in both the blood pressure and the 
volume of the respired air are excluded, as is the case in such experi- 
ments as these, then the increased amplitude of the respiratory waves 
seems to indicate that a larger volume of blood is passing through 
the lungs at any given time, and this, in turn, that a larger amount 
of blood is being returned to the right auricle through the systemic 
vessels. Of course the increased amplitude of these waves may have 
been due in part to the faults of the mercury manometer, that is, 
when the heart was beating more slowly the excursions of the 
column of mercury were increased so greatly by its inertia that the 
respiratory undulations were obscured, whereas with the more rapid 
rate the effects of the mercury’s inertia were less marked. But it does 
not seem probable that this change in the respiratory waves can be 
explained entirely in this manner, for not only are these waves 
often marked when the heart is beating slowly, but their amplitude 
is frequently increased by injecting a large amount of normal saline 
solution into the circulation, although no changes occur in the blood 
pressure and heart rate, or at least do not occur for some time after 
the changes in the respiratory waves. The increased amplitude of 
these waves after the injection of normal saline solution is almost 
certainly due to the larger amount of liquid in the vessels of the 
lungs; the same change occurring after stimulation of the accelera- 
tors is probably due to a similar cause. 
Finally the experiments of Stevens and Lee upon the action of 
intermittent pressure upon the blood vessels of the frog and terrapin 
suggest the possibility that the accelerators may, at times, play a 
part in maintaining the normal tone of the blood vessels. These 
authors found that “ a rhythmically interrupted force applied to the 
blood vessels of the frog and terrapin through the medium of a 
circulating fluid exerts a special action upon them, in consequence 
of which a constriction of them takes place; ” as a result of such 
action a much smaller amount of liquid supplied intermittently is 
needed to maintain a given arterial pressure than when the force 
is a constant one. No experiments were made to determine the 
number of interruptions which give the best results; it is probable, 
however, that this number would be found to differ in the case of the 
vessels of different organs, so that in some a rapid, in others a slow, 
rate would have the more marked effect. 
Rapid heart action of other than reflex origin. — There are many 
cases of rapid heart action of other than reflex origin upon which Acceleration of the Mammalian Heart. 
463 
the experiments described in this paper may throw some light; a 
few such cases will be considered briefly. 
Voluntary acceleration of the heart. — The power which some persons 
have of voluntarily increasing the heart rate has been studied with 
especial care by Tarchanoff1 and Pease,2 and more recently by 
Van de Velde.3 
Tarchanoff made a number of experiments in order to determine 
the cause of the acceleration, i. e. whether it is due to a diminution 
of the tonic activity of the vagi or to a stimulation of the accelerators; 
he reached the conclusion that the acceleration is due to a direct 
action upon the centres of the accelerator nerves. The grounds 
for this conclusion were three: (1) the manner in which the accelera- 
tion appeared and disappeared, (2) the changes in the form of the 
sphygmograms, and (3) the changes in the volume of the extremi- 
ties. Tarchanoff found that in the person upon whom he experi- 
mented, the maximum acceleration was reached only after one half to 
three quarters of a minute after the beginning of the effort to increase 
the heart rate; the return to the normal rate was also gradual. 
Comparing the slow development of the voluntary acceleration 
with the rapid development following the section of the vagi, Tar- 
chanoff drew the conclusion that the voluntary acceleration was 
due to the accelerator nerves. It does not seem to me that this 
argument is at all conclusive. It does not seem fair to compare 
the effect of section of the vagi, which causes an immediate effect 
on the heart rate, with the acceleration following a distinct effort of 
the will.4 
It has also been shown above that under certain circumstances the 
diminution of the tonicity of the vagus caused by the stimulation of 
a sensory nerve may be very slowly developed and very slowly dis- 
appear. Moreover, in one of Van de Velde’s patients the maximum 
acceleration occurred in the first 10 seconds of the effort; whereas 
Bohm in experiments upon animals found from the examination of 
a large number of tracings that w7hen the accelerators were stimulated 
directly the maximum acceleration occurred as a rule in the second 
1 Tarchanoff : Archiv f. d. ges. Physiol., 1885, xxxv, p. 109. 
‘2 Pease : Boston medical and surgical journal, 1889, cxx, p. 526. 
3 Van de Velde : Archiv f. d. ges., Physiol., 1897, Ixvi, p. 232. 
4 Van de Velde compares the effort necessary to cause acceleration to the feeling 
experienced when a person attempts to perform some unusual muscular movement, 
such, for example, as contracting the muscles of the ear, or flexing indepen- 
dently the last phalanx of the finger. 464 
Reid Hunt. 
io seconds of the stimulation. In the experiments of Pease also the 
latent period seems to have been very short; thus in some of the 
tracings given the first beat after the effort was made seems to have 
been shortened and the greatest acceleration to have occurred in 
the first two or three seconds, the entire effort continuing but five 
seconds. We certainly have no reason to suppose that the accelera- 
tors can be thrown into activity by an act of the will more quickly 
than when they are stimulated directly by the electric current. 
It is also worthy of note that in the case of Salome, upon whom 
most of Tarchanoff’s experiments were made, acceleration of the 
heart easily resulted from slight external causes, — a fact which, judg- 
ing from experiments upon animals, points to an unstable condition 
of the cardio-inhibitory centre. 
The second argument which Tarchanoff brings forward in support 
of his view — the changes in the form of the sphygmogram — seems 
to me to be still less conclusive, owing to the difficulty of interpret- 
ing these curves; in fact the changes which Tarchanoff adduces as 
evidence that the increase in the heart rate was due to the action of 
the accelerators are very nearly the same as those which Nothnagel 
brought forward to show that in some cases of rapid heart action the 
increase comes from a diminution of the vagus tonus. 
The third argument of Tarchanoff in support of the above view is 
that when the heart rate increased, the volume of the foot, as deter- 
mined by the plethysmograph, was not increased, although, accord- 
ing to Tarchanoff, an increased volume would necessarily have 
occurred as a result of the augmented blood pressure if the accel- 
eration in rate had been due to a diminution of vagus tonus; it is 
however, by no means uncommon for section of the vagi to cause 
acceleration of the heart without any increase in the blood pres- 
sure occurring — in fact there is sometimes a fall of general blood 
pressure. 
In the light of these considerations it seems to me that the evi- 
dence for the view that voluntary acceleration is due to the action of 
the accelerator nerves is entirely inconclusive; in fact I am inclined 
to think that the weight of evidence is rather in favor of the view that 
it is due to a diminution of the tonus of the vagi. 
Acceleration of the heart during muscular exercise. — The influence 
of the cardiac nerves on the increase in the heart rate during muscu- 
lar exercise has been most carefully studied by Hering.1 This author 
1 Hering, H. E. : Archiv f. d. ges., Physiol., 1895, lx, p. 429. Acceleration of the Mammalian Heart. 
465 
reaches the conclusion that the acceleration is due in part to an in- 
creased activity of the accelerator nerves, perhaps of reflex origin, 
and in part to a diminution of the tonic activity of the vagi caused 
by the increased respiratory movements. 
It seems to me that a careful examination of Hering’s experiments 
shows that the diminution of the tonic activity of the vagi is sufficient 
to explain his results, and that there is no clear evidence for believing 
in any increased action of the accelerators; the tonic activity of the 
latter nerves plays, however, a very important part here, as in the 
acceleration following stimulation of sensory nerves. Without going 
into too many details, the following observation on Hering’s experi- 
ments may be made. The average rate of the heart reached during 
muscular exercise in a number of experiments was 320 beats per 
minute, whereas the average rate during rest after section of the 
vagi was 321. Moreover, in one half of these experiments (see table 
p. 440) the maximum rate reached during exercise was less than or just 
the same as the rate in rest after the vagi were cut; in the other half 
of these experiments the maximum acceleration in exercise after the 
vagi were cut was less than 7 per cent. This acceleration of 7 per 
cent may have been due to a stimulation of the accelerator nerves, 
but it should be observed (1) that in other experiments (p. 476) in 
which both the vagi and accelerators had been cut a much greater 
acceleration (33 per cent and more) — due probably to changes in 
the respiration and blood pressure — was observed, and (2) that 
direct stimulation of the accelerators after section of the vagi may 
cause a much greater increase in the heart rate; the Cyons, for 
example, obtained an acceleration of over 50 per cent in such 
experiments. 
On the other hand Hering’s results show very clearly that the 
acceleration of the heart rate in exercise was much less after section 
of the accelerators; the average acceleration was but two-fifths as 
great as when they were intact. I think, however, that this difference 
can be attributed entirely to the removal of the tonic impulses of the 
accelerators. That the accelerators were in tonic activity in these 
experiments is made almost certain by the fact that when the vagi 
were cut after section of the accelerators there was but a slight 
increase in the heart rate; the greatest increase was 60 and the 
average 31 beats per minute, whereas in another series of experi- 
ments in which the vagi alone were cut the average increase was 122 
beats and the smallest increase (and this was a very exceptional case) 466 
Reid Hunt. 
was 68.1 It seems to me that these results, so far as the influence of the 
cardiac nerves is concerned, can be explained in exactly the same way 
as the acceleration following stimulation of a sensory nerve, namely, 
the essential factor in the acceleration is a diminution of the activity 
of the cardio-inhibitory centre; if the accelerator nerves are intact 
and in tonic activity the maximum rate reached is greater than when 
they are not in activity, but there seems to be no sufficient evidence 
for supposing that these nerves are thrown into increased action in 
muscular exercise. 
Athanasiu and Carvallo2 have also recently studied this question, 
and reached the conclusion that the essential factor in the accelera- 
tion is the reflex diminution of the activity of the cardio-inhibitory 
centre; their tracings also show that the latent period of the acceler- 
ation in muscular exercise is very short. 
MacWilliam,3 who believes the acceleration to be of vagus origin, 
has called attention to the fact that in those animals which are 
capable of long continued muscular exercise (such as the horse, 
dog, and hare) the vagi are in a condition of marked tonic activity, 
while in such an animal as the rabbit, which is not capable of so 
prolonged exertions, the tonic activity of the vagi is not so marked. 
Acceleration following compression of the carotids. — Cooper and 
Magendie stated that acceleration of the heart results from the com- 
pression of the carotid; this subject has been studied with especial 
care by Francois-Franck,4 who considered acceleration to be due to 
a stimulation of the accelerator nerves. Examination of the curves 
and the descriptions of the experiments of Francois-Franck show 
that in most cases the vagi were intact; in other cases nothing is 
said about the vagi. The curves published by this author are 
strikingly like the curves of reflex acceleration obtained by stimu- 
lating a sensory nerve after section of the accelerators; the second, 
and in some cases the first, heart-beat after compression of the carotid 
was shortened, and after the compression ceased the heart returned 
instantly to its previous rate or was slowed, the very first beat being 
1 Hering commented on the slight increase in the heart rate following section 
of the vagi after previous section of the accelerators, and recognized that the integ- 
rity of these nerves is an important factor in the acceleration following section of 
the vagi, but he seemed to hesitate to interpret his results as evidence for the 
tonic activity of the accelerators. (See also note on p. 397.) 
2 Athanasiu and Carvallo : Archives de physiologie, 1898, p. 561. 
3 MacWilliam : Proceedings of the royal society, London, 1893, liii, p. 476. 
4 Francois-Franck: Travaux du laboratoire de Marey, 1878-79, p. 74. Acceleration of the Mammalian Heart. 
467 
either of the normal length or prolonged. Francois-Franck noted the 
very short latent period as compared with the latent period when 
the accelerator nerves are stimulated electrically, and suggested that 
the difference may be due to the normal stimulus from the central 
nervous system acting differently from direct electrical stimulation; 
but there seems to be no evidence for this supposition. It is true 
that Francois-Franck states that no acceleration occurred after extir- 
pation of the inferior cervical and first thoracic ganglia; but such an 
operation, unless performed with great care, destroys the tonicity of 
the vagus centre. 
Many more cases of acceleration of the heart in which diminution 
of the tone of the vagi is probably the chief factor might be cited. 
Thus the acceleration accompanying each act of deglutition in man,1 
that occurring during each inspiration,2 and the increase in the heart 
rate when the lungs are inflated by a pair of bellows,3 all seem to be 
due to a diminution of the tonic activity of the vagi. The cause of 
the rapid heart rate observed in certain diseases,4 and after the admin- 
1 Meltzer : Archiv fur Physiologie, 1883, p. 223. 
2 Fredericq: Archives de biologie, 1882, iii, p. 86. 
3 Hering: Sitz.-Ber. d. kais. Akad. d. Wiss., math.-naturvv. Cl., 1871, lxvi, 
2, p. 348. See also H. E. Hering : Archiv f. d. ges. Physiol., 1895, lx, p. 461. 
4 The rapid heart action in paroxysmal tachycardia is sometimes referred to a 
diminution of the tonus of the vagus, sometimes to a stimulation of the accelerators; 
there seems to be little unanimity of opinion among those who have described this 
condition. The above experiments upon animals seem adapted to throw some light 
upon this subject. Unless we assume that the accelerator nerves of man are very 
different physiologically from those of the lower animals, it seems impossible to 
accept the view that in some cases of tachycardia the rapid rate of the heart is due 
to a stimulation of the accelerator nerves. Thus there are cases reported (by H. C. 
Wood, e. g. University medical magazine, 1890-91, iii, p. 273, and by Hochhaus, 
Deutsches Archiv fur klinische Medicin, 1893, li, p. 19) in which the rapid action of 
the heart ended instantaneously, the rate decreasing in one case from 184 to 78 per 
minute; experiments on animals show that stimulation of the accelerators is always 
followed by a long after-effect upon the heart. Again, the rapid action of the heart 
in these cases may continue for days, the heart beating continuously at double or 
more than double its normal rate; such an acceleration in animals can be maintained 
for but a very short time by powerful electrical stimulation of the accelerators. 
On the other hand, many of these cases can be easily explained by the diminu- 
tion of the tonus of the inhibitory nerves. I have shown above how easy it is to 
get the cardio-inhibitory centre into a condition of unstable equilibrium by the action 
of drugs, changes in blood pressure, respiration, etc.; I have also called attention to 
the fact that there are great individual variations, the centre being inhibited in 
some animals with ease, in others of the same species with difficulty. When the 
cardio-inhibitory centre is in such a condition of unstable equilibrium, very slight 468 
Reid Hunt. 
istration of drugs, is in many cases obscure; but there seems as yet 
to be no evidence inconsistent with the view that in these cases the 
action is, as a rule, either a direct one upon the heart itself or upon 
the cardio-inhibitory centre. 
Unusual difficulties are met with in investigating the effect of 
psychical influences upon the heart rate, but there seems to be no 
reason for supposing that the acceleration in such cases is different 
in origin from that in the cases which have been discussed above. 
Leaving out of consideration the cases in which the cause of the 
acceleration is doubtful, and admitting that in some of those dis- 
cussed above the acceleration is due in part to a direct action of the 
accelerator nerves, it must still be granted that decrease of the tone 
of the cardio-inhibitory centre is the most usual cause of an increase 
in the heart rate. 
When it is remembered what an important part inhibition in one 
form or another plays in other functions of the body, — how, for ex- 
ample, it seems to occur in every act of respiration,1 in every move- 
ment of a limb,2 how important it is in movements of the pupil,3 the 
regulation of the flow of the blood, the movements of the intestine, 
causes — a little ether or curare, weak stimulation of a nerve, a little operating, etc.— 
are sufficient to cause a marked acceleration of the heart; this acceleration may con- 
tinue for a long time. If we assume that in the patients who suffer from paroxysmal 
tachycardia the cardio-inhibitory centre is in an unstable condition (usually as an 
individual peculiarity, though this condition seems to be exaggerated at times by 
such influences as recent illness, excessive use of alcohol, coffee, etc.), it is easy to 
see how some slight change might bring on an attack. Among the exciting causes 
mentioned (see Probsting, Deutsches Archiv fur klinische Medicin, 1882, xxxi, 
p. 349, and Herringham, Edinburgh medical journal, 1897, i, p. 367) are sudden 
exertions or injuries, digestive and uterine disturbances — influences which might 
readily cause a reflex inhibition of the vagus centre. In some cases pathological 
changes of the pericardium and of the myocardium are described ; in the light of 
the experiments of Knoll upon the reflexes from the heart it is not improbable that 
such changes can cause a reflex inhibition of the cardio-inhibitory centre. That 
diminution of the tonic influence of the vagi is sufficient to account for the rapid 
heart observed in most cases of tachycardia follows from the effects of injuries to 
the trunk of the vagi; Edinger says that a heart rate of 240 per minute and more 
has resulted in man from such injuries — a rate which is not often exceeded in 
paroxysmal tachycardia. 
1 Meltzer: Archiv fur Physiologie, 1892, p. 340. 
2 Hering and Sherrington: Archiv f. d. ges. Physiol., 1897, lxviii, p. 222. 
Sherrington : Journal of physiology, 1899, xxiii, suppl., p. 26. 
3 Braunstein : Zur Lehre von der Innervation der Pupillenbewegung, 1894, 
p. 95. A cceleration of the Mammalian Heart. 
469 
etc.,1 it is not surprising that the body should make use of it in 
regulating the rate of the heart-beat. Not only can an increase in the 
heart rate be caused more quickly by an inhibition of the cardio- 
inhibitory centre than by a stimulation of the accelerator centre, but 
it probably involves a smaller expenditure of energy. Although the 
accelerator nerves take no direct part in the production of a more 
rapid heart-beat (z. e. they are not thrown into increased activity), 
yet it is largely in virtue of their tonic activity that inhibition of the 
vagus centre leads to such prompt results. 
Whether an inhibition of the accelerators leading to a slowing of 
the heart ever occurs is not known. It is not improbable, however, 
that changes in the tonicity of the accelerator centre occur, the 
tonicity being at one time increased and at another decreased, but 
there seems to be no evidence that such changes are ever produced 
suddenly, for example, as a result of a reflex act. 
Summary of Results. 
The chief facts brought out in this paper may be summarized as 
follows: — 
(1) The accelerator nerves of the dog, cat, and rabbit, and prob- 
ably of other mammals, are almost always in tonic activity; the tonic 
activity of the accelerators is not impaired by influences which abolish 
not only the tonic activity but also the irritability of many other nerve 
centres. 
(2) Under some circumstances the tonic activity of the accelerators 
is an important factor in maintaining the normal rhythm of the heart, 
and stimulation of them will sometimes cause an irregular heart to 
become regular; this action of the accelerator seems to be most 
marked in cases in which the irritability of the cardiac muscle has 
been reduced in some manner. 
(3) Stimulation of the accelerators, if excessive, will decrease the 
rate of beat, and make the heart more irritable to impulses reaching 
it through the vagi. Even death may result from the excessive stim- 
ulation of these nerves. 
These facts indicate that the stimulation of the accelerators can 
cause real fatigue of the cardiac muscle. 
(4) New evidence is afforded for the .view that the inhibitory and 
accelerator nerves are strictly antagonistic ; this antagonism applies to 
1 For other illustrations of inhibition, see Meltzer: Archiv fur Physiologie, 
1883, pp. 225-235. 470 
Reid Hunt. 
both systole and diastole, but with the same strength of current the 
systole is more easily influenced by stimulation of the accelerators, 
and the diastole by stimulation of the inhibitory nerves. 
(5) The tonic activity of the accelerators limits the tonic activity 
of the inhibitory nerves, and vice versa ; the normal heart rate, so far 
as this is governed by the extra-cardiac nerves, is determined by the 
impulses reaching it simultaneously through these two channels. 
(6) The inhibitory nerves exert a protective influence over the 
heart; not only do they restrain the action of the accelerators, but 
their stimulation seems to improve the condition of the heart. 
(7) The view that reflex acceleration is caused by inhibition of the 
cardio-inhibitory centre is confirmed; no evidence could be found 
that the accelerator nerves are ever thrown into action reflexly. 
(8) The tonic activity of the accelerator nerves exerts a modifying 
influence over reflex acceleration; the maximum acceleration is 
greater, and is longer continued, and there is less tendency to a 
subsequent slowing when these nerves are intact. 
(9) There are probably in most nerve trunks two varieties of 
nerve fibres to the cardio-inhibitory centre; one variety causes an 
inhibition, the other an excitation of this centre. When a nerve is 
crushed the former variety regenerates earlier than the latter. 
(10) The most important functions of the accelerators seem to be 
connected with their tonic activity; aside from this their functions 
are obscure, but it is not improbable that by altering the rate of the 
heart-beat they exercise an important influence upon the circula- 
tion through certain organs. 
(11) It is very probable that almost all cases of rapid heart action 
are due to a diminution of the tonic activity of the cardio-inhibitory 
centre.