Amyl Nitrite, 
A Powerful Cardiac StWiilant. 
EDWARD T. REIMERT, M.D. 
BY 
REPRINT FROM 
Nch) Yotfe Ittcbical JStmvnal 
antt ©bstctrical I&cbieto, 
July, 1881. This Paper is reprinted from The New York Medical Journal 
and Obstetrical Review for July, 1881. 
The contents of that number are as follows: 
page 
Yaughan’s Chemical Physiology and Pathol- 
ogy 62 
Clowes’s Practical Chemistry 63 
Da Costa’s Medical Diagnosis 64 
Kane on Drugs that Enslave < 64 
Seguin’s Report on Education 64 
Lee’s Hand-Book for Coroners 65 
Freire’s Travaux Chimiques 66 
Deems’s Urinary Analysis 66 
Rooks and Pamphlets received 66 
The Corpuscular Elements of the Blood ; their 
Anatomy and Physiology, Normal and 
Pathological. By Alexander Duane, 
M.D 1 
The Development of the Eye. By William 
C. Ayres, M.D 17 
Amyl Nitrite, a Powerful Cardiac Stimulant. 
By Edward T. Keichert, M. D., etc., 
Newark, N. J 33 
Coup de Fouet, or Rupture of the Plantaris 
Muscle. By A. B. Judson, M. D 40 
©rtginal Communications. 
PAGE 
JSJrocecbtnfis of 
U tutorials. 
New York Obstetrical Society 67 
American Influence in Gynaecology 44 
ilcports on tije progress of fSlelncme. 
Monthly Report on Obstetrics and Gynaecol- 
ogy. By Trank P. Poster, M. D., etc.. 73 
Quarterly Report on Ophthalmology and Otol- 
ogy. By diaries Stedman Bull, M.D., 
etc 87 
Semi-annual Report on Psychological Medi- 
cine. By Norton Polsoni, M. D., Bos- 
ton 104 
Purulent, Croupous or Membranous, and 
Diphtheritic Conjunctivitis in Infants. By 
Charles Stedman Bull, M. D 45 
Special Slrticlcs. 
a&cbictos anb Htterarg Xotcs. 
Fliigge’s Lehrbuch der hygienischen Unter- 
suchungsmethoden. 55 
Duhring on Diseases of the Skin 59 
Warren on the Column® Adiposae 61 
Seiler’s Compendium of Microscopical Tech- 
nology 62 
l&isccUann. 
Therapeutical Notes.— Belladonna; Carbolic 
Acid 109 
London International Exhibition 11l 
Army Intelligence 11l 
The New York Medical Journal and Obstetrical Review 
is published monthly, and contains 112 closely printed octavo pages. 
It is devoted to the general practice of medicine, and aims to meet 
the wants of the general practitioner. 
edited by 
PHYSICIAN FOR DISEASES OF WOMEN TO THE OUT-PATIENT DEPARTMENT OF THE NEW 
YORK HOSPITAL. 
FRANK P. FOSTER, M. D., 
New York: D. APPLETON & CO., Publishers, 
Single Number, 40 Cents. 
1, 3, & 5 BOND STREET. 
Yearly Subscription, $4.00, AMYL NITRITE, A POWERFUL CARDIAC STIMULANT. 
EDWARD T. REICHERT, M. D., 
FORMERLY DEMONSTRATOR OF EXPERIMENTAL THERAPEUTICS AND INSTRUCTOR IN EXPERIMENTAL 
PHYSIOLOGY IN THE POST-GRADUATE COURSE OF MEDICINE IN THE UNIVERSITY 
OF PENNSYLVANIA. 
The action of digitalis on the heart was, for many years, invested 
in doubt, and it was a disputed point between two factions of thera- 
peutists as to whether it was a cardiac stimulant or a cardiac de- 
pressant, and it was not until the experimental therapeutist came to 
the foreground, with his convincing evidence, that this vexed ques- 
tion was finally decided, and the drug placed in its proper physio- 
logical classification. The amyl nitrite seemed prone to undergo a 
similar controversy, for, on looking over the literature on the sub- 
ject, opinions are found which are as diverse as they well could be, 
and deductions made which are inconsistent with the results of 
experiments, and contrary to facts revealed by a more thorough 
consideration. Wood (“Therapeutics,” 1879, p. 348), after study- 
ing carefully the experimental papers accessible, concludes that 
“the whole evidence seems to show that the sudden, thumping, 
rapid stroke of the heart which is so clearly produced by the nitrite 
of amyl in man is due, at least in part, to a depression of the inhib- 
itory cardiac nerves” ; and, in a previous paper, he gives as another 
factor the diminished oxidation the nitrite causes, and a thrill of 
impending suffocation and accelerated pulse due thereto; but this 
will be referred to more fully later in my paper. 
' While this statement is in the main correct, because there can 
be no doubt that the nitrites both depress the inhibitory appa- 4 
ratus and diminish oxidation, yet I believe that there is still 
another and more important factor, therapeutically, concerned in 
this increase of the heart’s action, as was stated in a recent paper on 
the potassium nitrite (“Am. Jour, of the Med. Sci.,” July, 1880), 
in which I claimed that the nitrites, in small or moderate doses, 
acted as direct cardiac stimulants, and, moreover, gave the results 
of a series of experiments with the above-mentioned salt, and 
endeavored, while discussing its physiological action, to clearly 
show wherein the deductions of certain observers of the action of 
the amyl compound had been erroneously drawn, and why the 
results of certain of the experiments undoubtedly corroborated my 
belief. I have accordingly resumed a discussion of the subject 
and have carefully reviewed the accessible papers in this relation, 
and will consider the evidence deduced under two heads—physio- 
logical and clinical. 
Referring to the physiological papers, vve find that Pick (“ Cen- 
tralbl. f. d. tried. Wissensch.,” Berlin, 1873, ISTo. 55) declares that it 
causes a relaxation of the heart muscle, and that the accelerated 
action of this organ is, in part at least, due to the opening of the 
vascular channels ; that Filenhe (Pfliiger’s “ Archiv,” Bd. ix, p. 490), 
by the result of a single and very interesting experiment, indicated 
that the increase of the cardiac heat was due alone to a depression 
of the vagi nerves, for it was found in this experiment that after 
section of these nerves, an electric current being employed by direct 
application to the peripheral portion of the severed trunks, of such a 
strength as to lower the pulse rate to the normal, the increase did 
not occur as in normal animals; that Mayer and Friedrich (“Arch, 
f. exper. Path. u. Pharm.,” 1875, v, p. 55) in a different way corrobo- 
rated Filenhe’s testimony, for they observed that sudden asphyxia 
did not slow the pulse after the administration of the nitrite as it 
did in normal animals, and, moreover, when they pressed the carot- 
ids, and prevented the blood from gaining access to the cerebral 
arteries, the increase did not occur, nor did they find any diminu- 
tion of the pulse rate by endeavoring to induce a reflex inhibition 
of the heart by irritating a sensory nerve. 
Wood (“Am. Jour, of the Med. Sci.,” 1871, 1, p. 422) states 
that, so far from being a cardiac stimulant, it is a direct depressor 
of the circulation, because, although it increases the number of the 
beats, it never increases the force ; and in a later and more elabo- 
rate article, based upon the results of a direct series of experiments 
on animals (ibid., 2, p. 39), concludes that it “ does not act upon 
the heart until a considerable point of saturation of the blood and 
system is reached,” and that the heart is then depressed (p. 53). 5 
He did not at this time make any experiments directly to decide 
what the cardiac action of the poison was, except in determination 
of the local action on the exposed heart of the frog in toxic 
amounts, when he found, after placing a few drops on that organ, 
that its action speedily became arrested. In a more recent article 
{ibid., 1871, 2, p. 359) a discussion of the subject is resumed, and 
he theoretically explains the “excited, violent, and labored action” 
of the heart in this way: “ when the nitrite is taken into the lungs 
it instantly arrests or diminishes oxidation, and a thrill of impend- 
ing suffocation runs through the system, in obedience to which the 
respiratory and circulatory systems gather up and exert to the 
utmost their forces. The central impulse sent to the cardiac and 
respiratory muscles is at first much more than sufficient to over- 
come any direct action of the nitrite upon them, but, the inhala- 
tion being persisted in, the impulse is constantly growing weaker, 
and the direct influence of the drug stronger, so that there soon 
comes a time when the reverse is true, and the heart’s power is 
more or less nearly extinguished.” 
Dugau (“ Rev. Mens, de Med. et de Chir.,” July, 1880; quoted 
in “ London Med. Record,” Aug. 15, 1880, and “ Am. Jour, of 
the Med. Sci.,” Oct., 1880, p. 554) concludes, from the result of an 
elaborate series of experiments, that the nitrite acts upon the heart 
after all the nerves have been severed; that strong doses cause a 
diastolic arrest, and that the acceleration of the heart beat seems to 
be in relation with the fall of arterial tension, for it occurred after all 
nervous connection of the heart with the central nervous system was 
severed. Brunton (“ Med. Times and Gaz.,” 1870, i, p. 320) found 
that the nitrite did not diminish the work done by the heart in a 
given time, although it decidedly increased the frequency of its con- 
tractions. The frequency he is inclined to attribute to a depres- 
sion of the inhibitory nerves, because it was more apparent in dogs, 
in which the vagal apparatus is more sensitive than in rabbits 
(“Jour, of Anat. and Physiol.,” v, 1871, p. 92); but he did not 
make any experiments to specially determine how the pulse was 
affected, and his deductions, as may be inferred, are based upon 
theoretical grounds alone. In experiments on the blood pressure 
he found the same decided diminution as is noted by other observ- 
ers, but in Seven experiments in which the aorta was compressed 
immediately below the diaphragm the pressure was not reduced as 
in normal animals, for a primary rise occurred which equaled about 
oneffth the normal, and which preceded a marked fall. Moreover, 
in three other experiments, in which the spinal cord was cut and 
the aorta compressed as before, a similar result was recorded. He concludes that the diminution of the arterial tension was vaso- 
motor and not cardiac, but, unfortunately, he does not discuss the 
cause of the increase in animals with the aorta compressed. 
In reviewing the results above recorded, and the deductions 
made therefrom by the different investigators, we find, indeed, quite 
a diversity of opinion to deal with. If we first consider the theories 
of the modus ojperandi of the action on the pulse, much in the 
papers of Filenhe, Mayer and Friedrich, and Brunton goes to 
show that the nitrite does depress the vagal apparatus and increase 
the pulse in this way; yet, evidently, this does not cover the ground, 
according to Pick’s opinion, nor those of Wood and Dugan. Al- 
though experimenters almost universally agree that the heart is 
ultimately slowed and paralyzed, yet, as we see, they do not agree 
as to how the frequency is affected, and when we come to examine 
their papers it is found that Filenhe, Mayer and Friedrich, and Du- 
gan were the only ones who made experiments in direct determina- 
tion of this point, and the deductions of the first three observers 
must be accepted with allowance because of the very indirect, but 
no less ingenious, way in which they sought to decide this action. 
Yet it seems we must admit that the vagi apparatus is de- 
pressed, and that the increased action of the heart is at least par- 
tially in this way effected. Wood’s theory is indeed a beautiful 
and masterly one, and well worthy of my illustrious friend and 
teacher, but, unfortunately, it has been founded rather upon hy- 
potheses than direct experimentation. Pick’s is logical enough, for it 
is a truism that there is a compensatory relation existing between the 
action of the heart and the condition of the vaso-motor system, and 
that when the vascular channels are open the heart will naturally 
beat faster in endeavoring to overcome the excessive drainage, and 
vice versa. Dugau’s view closely coincides with this, but where he 
was misled was in not isolating the action on the vaso-motor system 
from that on the heart, as we shall presently see, 
Pegarding the action on the arterial pressure, it is almost uni- 
versally conceded that the marked diminution is both vaso-motor 
and cardiac, the latter factor coming in late in the poisoning, as is 
believed by both Wood and Brunton. If this is so, it must be cer- 
tain that the early fall of pressure is entirely vaso-motor. 
If, now, it were possible to eliminate the action of the nitrite on 
the heart from its action on the vaso-motor system, we could readily 
determine just how far the acceleration of the heart’s beat was af- 
fected by this diminution of pressure occurring from vaso-motor 
dilatation, as well as determine how the amount of work done by 
the heart is influenced. This identical thing was done, although 7 
imperfectly, in Brunton’s seven experiments when he pressed the 
abdominal aorta immediately below the diaphragm, and in the 
three later ones, in which he compressed the aorta and made section 
of the spinal cord; for it must be certain that, when the aorta was 
firmly pressed upon, the action of a large portion of the vaso-motor 
peripheries was practically paralyzed, because they were unable any 
longer to affect the arterial tension, and this was even further in- 
creased in the animals in which a section of the cord was made, 
which, of course, practically annihilated the vaso-motor centers in 
the medulla oblongata. ISTow, it must be equally as clear that, if 
we thus have the action of the vaso-motor system practically abol- 
ished, and the disturbing influences of the respirations or struggles 
overcome by curarizing the animals, as was also done, any change 
in the arterial tension which occurs will be the resultant of a direct 
cardiac action. What was the result in each of these ten experi- 
ments? In every one of them there was a primary and marked rise 
of pressure, which equaled as much as a fifth of the normal. It, 
therefore, must be apparent that this curious change in the results 
must be due to a direct cardiac action and an effect of a direct 
increase of the heart’s power. If we now admit Dugan’s evidence 
that the heart’s action is increased after severance of all central 
nervous communication, it is conclusively proved that the increase 
of arterial tension is due to a direct stimulation of the heart, in- 
creasing both its frequency and the amount of work performed. 
Why Brunton, Pick, and Dugan did not reach a similar conclusion 
is, it is obvious, simply because they did not eliminate the vaso- 
motor from the cardiac action. It is also clear from the foregoing 
that the acceleration of the pulse must also in part be cardiac. 
In a paper on the potassium nitrite, previously referred to, I 
claimed that the nitrites all affected the economy in a similar man- 
ner, and that, although it was found that the potassium salt caused 
a primary rise of pressure preceding the diminution, which was an 
entirely different result from that obtained on normal animals with 
the amyl nitrite, yet briefly it was explained in this way—that the 
nitrites acted in two ways to affect the blood pressure, the one by 
directly stimulating the heart, and the second by depressing the 
vaso-motor system, the centers especially ; that the stimulating 
effects on the heart ultimately gave way to depression ; and that the 
reason why the amyl nitrite did not cause a rise of pressure, like the 
potassium salt, was because its vaso-motor action was comparatively 
more intense, and was more than sufficient to overcome the stimu- 
lant effect on the heart, which was finally indicated to be a fact by 
a comparison of the results of Brunton’s experiments and my own. 8 
It was further clearly demonstrated that the potassium nitrite caused 
at least a part of the increased frequency of the pulse by a direct 
stimulation of the heart, and probably by a consentaneous depres- 
sion of the inhibitory centers. 
If, therefore, we accept these deductions as made from the re- 
sults of Brunton’s and Dugau’s experiments, it will be obvious that 
the action of the amyl nitrite is identical with that of the alkaline 
salts, and, consequently, that it is a direct cardiac stimulant, increas- 
ing the frequency of the heart’s action and the amount of work 
done in a given time. 
If we now look into the clinical history of this interesting com- 
pound, we find that there is no paucity of evidence to support this 
belief, but, indeed, that cases illustrating it are so numerous that, 
even without the experimental evidence as above deduced, we could 
arrive at no other conclusion. For instance: 1, there can be no 
possible doubt that chloroform is a direct and powerful depressant 
of the heart, and that in toxic amounts it seriously diminishes the 
powers of this organ and causes death in a vast majority of cases 
by this paretic action; 2, that it is a conceded fact that in collapse 
and syncope the depressed condition of the heart is a marked symp- 
tom ■; 3, that in certain forms of heart disease, whether there be a 
condition of fatty degeneration, valvular insufficiency without com- 
pensating hypertrophy, or simple dilatation, the heart’s powers are 
enfeebled and we have the occurrence from time to time of parox- 
ysms of distress, which are undoubtedly due to a further depression 
of its working capacity. It is, therefore, evident that in each of the 
above-mentioned three divisions we have an unmistakable condition 
of cardiac depression, which, in the last of them, is frequently and 
decidedly evinced in the paroxysmal attacks which recur from time 
to time ; and it must be apparent that the administration of cardiac 
depressants in such conditions of the system would be attended with 
harm, if it did not materially aggravate the symptoms or induce 
death—for who would think of giving aconite or tartar emetic in 
cardiac syncope, or when a patient was cold, cyanosed, and gasping 
for life’s breath in a paroxysm of heart pang?* Did the amyl 
have no further primary effect on the heart than to simply increase 
its frequency by a depression of the vagi apparatus or by inducing 
it through a diminution of the arterial tension and without affect- 
* An apparent exception to this is the use of hydrocyanic acid, but this is given in 
such small amounts that only its primary effect on the circulation is obtained, which is a 
slowing and increased fullness of the pulse, due to a stimulation of the inhibitory nerves, 
and accompanied by a slight rise in pressure, the depression of the heart and fall of 
arterial tension being a secondary effect. 9 
ing the amount of work done, it would seem certain that in such 
cases as above quoted either its value as a therapeutic agent would 
be nil, or else it would even aggravate the symptoms, since its 
only admitted action on the heart, besides the increased frequency, 
is a depression of its powers and ultimate diminution of its pul- 
sations. 
Now, what does the clinical history teach us of the action of the 
nitrite in chloroform poisoning? Browne (“Med. Graz.,” June 11, 
1870) believes that it seems worthy of a trial in chloroform narcosis 
because its use is followed by a marked acceleration of the heart 
and flushing of the face. Boder (“ Lancet,” May, 1875 ; quoted in 
“ Proc. of the Med. Soc. of the County of Kings,” Brooklyn, N. Y., 
1875) gives three cases in which dangerous and alarming symptoms 
of the effects of chloroform were instantly and effectually overcome. 
Hinton (“Phila. Med. Times,” v, 1875, p. 694) cites another illus- 
trating its stimulant effects; and Burrall (“ Lancet,” May, 1875), 
Schuller (“ Med. Times and Gaz.,” Dec. 13,1874), and Lane (“ Brit. 
Med. Jour.,” 1877, i, p. 101) reiterate this statement. The latter 
observer concludes that when it is inhaled in small quantities it 
produces recovery from chloroform insensibility, and that this is due 
to a removal of the cerebral anasmia by the dilatation of the arte- 
rioles, to the raising of the temperature of the body, and the removal 
of the paralysis of the heart. Solger (“Wien. rned. Presse,” Feb., 
1875) furnishes further evidence of the antagonism of the action of 
the amyl and chloroform; and Dabney (“ Richmond and Louisville 
Med. Jour.,” June, 1874) and Smart (“ Detroit Bev. of Med.,” x, 1875, 
p. 661), in experiments on animals, further testify to its efficiency. 
Dabney states that three animals out of four in chloroform insensi- 
bility recovered when death was apparently imminent, and that it 
produced a decided increase of both the force and frequency of the 
heart. Further, a very interesting experiment of ray own, showing 
the powerful stimulant effects of the nitrites on the heart, is given in 
a recent paper on the Ethylene Bichloride (“ Phila. Med. Times,” 
May 21, 1880), in which the heart was so seriously depressed that 
the pulsations were imperceptible to the touch, and the pulse-curve 
tracing was but a mere streak, no oscillations being apparent; yet 
after giving the amyl the heart’s action was recovered with aston- 
ishing rapidity.* 
Jones (“Practitioner,” vii, 1871, p. 213) gives a case of syn- 
* These last references, which properly belong to the physiological papers, are given 
here because of their bearing such a close relationship to the clinical papers on the same 
subject. 10 
cope in which the radial pulse was scarcely to be felt, and when the 
nitrite was given it caused it to beat rapidly and full. From the 
rapidity with which the patient recovered he concludes that the 
syncopal condition would have continued longer but for the ether. 
Minor (“ Virginia Med. Monthly,” iv, 1878, 1876) used it in a case 
of locomotor ataxia when the patient was in a condition of impend- 
ing death, there being a hippocratic expression, stertorous and irregu- 
lar breathing, complete unconsciousness, an imperceptible cardiac 
impulse, and cold, clammy extremities. The amyl was given by 
inhalation, but with no effect, and it was therefore repeated hypo- 
dermically, three minims being used; and in a few moments “ the 
heart responded, as evinced by the appearance of a more natural 
hue of the cutaneous surface. The pulse was recognized in the ra- 
dial artery. Respiration became better.” The temperature was 
restored, and the patient responded to a pinch, which before was 
unnoticed. By repeating the dose the pulse became incompressi- 
ble. As much as fifteen minims was given hypodermically at once. 
Another exceedingly interesting case is cited by Madden (“Prac- 
titioner,” xii, 1874, p. 295) of a woman who suffered with severe 
and intractable menorrhagia, and who at the time referred to in his 
article was apparently dead. Upon using the amyl nitrite the 
respirations and circulation became fairly established and conscious- 
ness was subsequently restored. Moreover, whenever she appeared 
to be falling into this collapsed condition the amyl was resorted to 
with the happiest results ; hence, he thinks that this case “shows in 
a remarkable manner the power which the nitrite possesses to rouse 
the heart which has almost ceased to beat.” 
Two cases of fatty heart serve to further illustrate this stimulant 
action and the beneficial results, as a consequence, from its use. The 
first is that of Osgood (“Am. Jour, of the Med. Sci.,” 1871, 2, p. 360), 
who found it to act with remarkable efficacy, and so much so that he 
believes that death would have ensued in a few moments if it had 
not been given. The second case is one of Janeway’s (“ U. Y. Med. 
Jour.,” xx, 1874, p, 58), in which, after the complete extinction of 
the radial pulse, the nitrite caused it to become full. There are 
also two cases of valvular disease. Wood (“ Am. Jour, of the Med. 
Sci.,” 1871, 2, p. 361) states that in his case the effect of the drug 
in relieving the pang when other remedies failed was astonishing ; 
and Jones (100. cit.) tells us of a woman who suffered from cardiac 
dyspnoea, with a dilated hypertrophy of both ventricles (the dilata- 
tion being in excess), a feeble circulation, extreme anasarca, pul- 
monary oedema, lividity of the face, and shortness of breath. The 
use of the amyl nitrite produced most beneficial effects and induced 11 
a pleasant glow all over the body, and on each occasion of its use 
she felt easier and more comfortable about the chest. 
In reviewing all the foregoing facts, I think doubt can no longer 
exist that the amyl nitrite, like the alkaline salts, acts as a powerful 
and direct cardiac stimulant, increasing both the frequency of the 
heart’s pulsations and the amount of work done in a given time. 
106 Halsey Street, Newark, N. J., June, 1881.