Reprinted from the 
Philadelphia Hospital Reports, 
Yol. I, 1890. 
TWO CASES ILLUSTRATING THE THERAPEUTIC 
USES OP THE NITRITES 
SOLOMON SOLIS-COHEN, M.D, 
The following cases are briefly reported in illustration of the 
therapeutic uses of the nitrites ; 
Case L—Large doses of nitrites in a case of angina pectoris: psychic effect of inert 
medication.—Eobert Gallagher, aged 63, laborer, single, native of Ireland, was 
admitted December 11, 1889. The following notes of bis history were made by 
Dr. Harris, resident physician : 
“ He has always been a hard-working man, exposed to all vicissitudes of tem- 
perature and weather ; has used alcohol in moderation, but has never lost any time 
from work through drink. There is no venereal history. When a child he had 
chicken-pox, measles, small-pox and whooping-cough ; at 19 years of age, typhus 
fever ; and at 20, typhoid fever. At 33 years, an attack of acute inflammatory 
rheumatism confined him to bed for a number of weeks. Between the ages of 16 
and 20 he had occasional attacks of syncope, which lasted for a few minutes. 
There were no epileptiform convulsions and no aura. In 1862 he came to this 
country and remained apparently in good health until 1884, with the exception of 
an, attack of pleurisy and the following accidents : fracture of leg in 1872 ; fracture 
of skull in 1878, and three attacks of mild sunstroke. In 1884, while walking 
home from his work, he was suddenly attacked with sharp, stabbing pain in the 
left side, over the region of the heart, accompanied with what he called ‘sprinkles 
of pain ’ running up the neck. The pain quickly passed ;he did not fall or lose 
consciousness. Shortly afterward the attack was repeated, being, however, much 
more severe. He felt as if his heart were being compressed between two hands, 
and as if he were being smothered by a weight upon his chest. There was a sense 
of impending dissolution. This attack also passed over quickly, but left him too 
weak to return to work for two days. A repetition of the attack occurred in two 
weeks. This time the pain ran into the left arm, giving the sensation of ‘sprink- 
ling ’ and numbness. Since that time, the paroxysms have been more frequent 
and more severe ;he has been growing weaker ; his appetite is foiling. During 
nocturnal attacks he frequently loses consciousness for several minutes. There is 
no sensation of clutching at the throat, but the difficulty in breathing seems to be 
entirely in the thorax. The pain at times runs along the left shoulder and the 
back of the neck, terminating at the left mastoid process.” 2 
THERAPEUTIC USES OF THE NITRITES. 
After admission to the hospital, the attacks recurred almost daily, sometimes 
twice or oftener in the twenty-four hours. They were of two varieties, the more 
severe ones being followed by syncope and lasting longer than the others, which he 
termed “choking spells,” and which consisted of paroxysms of cardiac distress 
and dyspnoea. 
The patient noted that there was much less tendency to attack when the stom- 
ach was comparatively empty, and after meals he had always more or less pain 
and discomfort, though not amounting to a paroxysm. 
His mother died of some spasmodic pulmonary affection at the age of 76 ; his 
father died of apoplexy at 75 ; one sister died from a heatt trouble like his own, 
so he says, and one from old age. He has one sister living in Ireland and one in 
Philadelphia, who have attacks similar to his own. 
When I took charge of the case, January 16, 1890, physical examination 
showed no pulmonary lesion, no prominence of the pnecordium, no thrill, no visi- 
ble apex beat. Upon percussion the heart dulness appeared to be slightly less 
than is usually found. The first sound of the heart was rather feeble and deficient 
in valvular tone. The second sound was good, therefore relatively accentuated. 
There was no murmur. The radial arteries were rigid ; the temporal arteries 
tortuous, plainly visible and rigid. There was a marked arcus senilis. The face 
was anxious and haggard. 
Urinalysis repeatedly made, failed to show either albumin or sugar. Urates 
and phosphates were constantly in excess. 
The diagnosis of angina pectoris, the result of arterio-sclerosis, seems to be 
beyond reasonable doubt. While there was no evidence that either the sunstrokes 
or fracture of the skull had given rise to permanent cerebral lesion of a nature to 
account tor the symptoms, there was undoubtedly a strong general neurotic 
element in the case, so that the frequency and, in part, the severity of the attacks 
had been increased by fear. 
The treatment which had been instituted consisted of rest in bed, regulation of 
diet, due attention to the secretions and excretions, inhalation of amyl nitrite at 
the time of attack, and the administration of one drop of the centessimal solution 
of nitro-glycerin three times a day. I ordered the nitro-glycerin to be increased 
one drop at a dose, until physiological effects were obtained. After the dose had 
been raised to five minims three times a day, the patient remained for four days 
free from an attack. The paroxysmsihen recurred, and seeming to be uninfluenced 
by further increase of the drug per )*•*>, it was administered hypodermatically in 
doses of ten minims of the centessimal solution once, then twice, and finally three 
times daily. The attacks were partially controlled by this measure, so that a 
period of two weeks of comparative freedom was obtained before their recurrence ; 
which, however, ensued upon the diminution of the number of hypodermatic 
injections to two in twenty-four hours. 
Sodium nitrite was then administered internally, beginning with one-fourth of a 
grain and increasing the amount one-fourth of a grain at each dose, until finally a 
dose of five grains, three times a day, was reached. Under the administration of 
fifteen grains of sodium nitrite by the mouth, and forty minims of the centessimal 
solution of nitro-glycerin hypodermatically, in the twenty-four hours, the periods 
of quietude increased; though for a few days the tendency to continuous 
repetitions of the paroxysms during the night became so marked, following 
some mental disturbance, that even this active treatment had to be supplemented 
by the hypodermatic use of morphine with atropine at 8 o’clock, for several nights. THERAPEUTIC USES OP THE NITRITES. 
3 
There having been no recurrence of paroxysms since April 16, during the last 
week of April the hypodermatic injections were reduced to one per diem, and the 
amount of sodium nitrite cautiously decreased. Improvement in the patient’s 
condition continuing despite the mitigation of the treatment, and the hysterical 
element becoming more marked, it was decided to substitute for the nitrites hypo- 
dermatic injections of distilled water and pills of althea, without allowing the 
patient to be aware of the change. Improvement continued, so that the patient 
was successively able to get out of bed, to go around the ward and then the cor- 
ridors in a rolling chair, and then to walk out for exercise. The hypodermatic 
injections were soon discontinued, but the pills were not withdrawn until some 
time in August, on account of the mental distress occasioned by tentative with- 
drawal. Sodium iodide and arsenic were then used, the indication being the con- 
dition of the arteries. In September, no recurrence having taken place, the 
patient was transferred to the out-wards. 
The chief points of interest in this case are 
1. The large doses of the nitrites required to bring the affec- 
tion under control. 
2. The mental effect, when this control had been secured, of 
inert medication. 
3. While the patient was taking his largest doses of active 
medicaments, the only perceptible physiological effect was a very 
occasional and quite transient flushing of the face. 
Case ll.—lnfluenza in a patient having chronic valvular disease. (Mitral incompe- 
tence and aortic stenosis). Treatment by atropine and strychnine, with amyl nitrite.— 
William Hayward, aged 54, white, birth place Wales, residence Philadelphia, was 
admitted January 13, 1890, Ten days previously he had had slight chills, followed 
by slight fever. A few nights before admission he was picked up in the street uncon- 
scious. On admission he complained of pain in the left side of the chest, varying 
in intensity and situation. There was slight cough with scanty expectoration, 
which at times was tinged with blood. Temperature was 100°; pulse 100 ; respira- 
tions 32. 
Diagnosis of catarrhal pneumonia, probably influenza, was made by the resi- 
dent, Dr. Harris, who also recognized the chronic cardiac lesions to be described 
later. He was treated with digitalis and ammonium carbonate, a cotton jacket 
and turpentine stupes applied to the chest, alcohol freely administered. 
This treatment was continued until the 16th, when I took charge of the wards. 
At that time the temperature, which had pursued an irregular course, falling as 
low as 96.4°, and rising as high as 102°, was 97° in the morning ; the respirations 
were 44 and the pulse 76. The pulse and respirations had been as irregular as the 
temperature, the respirations varying between 28 and 56, the pulse always small 
and feeble, ranging between 48 and 80, though—probably under the influence of 
the digitalis—its usual range was below 60. There were at this time irregular 
areas of dull percussion over both lungs, more especially on the right; and at the 
right base quite a large patch corresponding probably to one-fourth of the lower 
lobe. The respiratory murmur was feeble throughout, and in situations corres- 
ponding with the dull percussion the auscultation signs varied from bronchial 4 
THERAPEUTIC USES OP THE NITRITES. 
breathing, on the one hand, to absence of breath-sounds, on the other. Bolh crepi- 
tant and sub-crepitant rales were present in varying distribution ; the crepitant rales 
being principally confined to the area of apparently lobar condensation at the 
right base, immediately above which, pleural friction was plainly perceptible. 
There was no evidence at any time of effusion. 
Palpation in the prrecordial region showed the apex of the heart in the sixth 
interspace and the nipple line. Just above this a systolic thrill was easily per- 
ceptible, limited to an area of about the size of a dime. The impulse was feeble 
and heaving and visible in two interspaces. Percussion showed increase of cardiac 
dulness toward the right, reaching nearly to the right border of the sternum. At 
the apex, a blowing murmur, rather low-pitched, replaced the first sound of the 
heart; the second sound was not audible. This murmur was transmitted into the 
axilla, and could be plainly heard below7 the posterior inferior angle of the scapula. 
Occasionally an indistinct murmur was heard before Hie systole, just above the apex. 
Over mid-sternum and over the aortic cartilage, a systolic murmur, harsher in 
quality and higher in pitch, was heard, and was transmitted into the arteries of 
the neck. The second sound could not be heard, but was replaced by an indistinct 
murmur. The differences in pitch and quality betw7een the aortic and mitral mur- 
murs were quite easily recognized, so that there was no difficulty in determining 
the coincidence of mitral incompetence and aortic obstruction with accompanying 
regurgitation, both evidently chronic conditions. No history of rheumatism was 
obtainable in explanation of this, though the patient had been a soldier and sub- 
ject to much exposure. There were histories of syphilis and of gonorrhoea. The 
patient had been short of breath, more or less, for ten years, especially upon exer- 
tion, so that he had not been able to do much work during that period. There 
had never been any dropsy; there was no albumin in the urine ; the lips were 
quite blue ; the face pale, pinched and anxious ; the nails blue ; the skin cold. 
Diagnosis of the acute condition was influenza, combined lobar and lobular pneu- 
monia. The digitalis was stopped and the patient placed upcn atropine sulphate, 
of a grain, with strychnine sulphate, of a grain, every five hours ; nitrite of 
amyl, five drops in alcohol, by the mouth, every three hours. Ammonium carbonate 
was continued, ten grains being given every hour at first, afterwards at longer inter- 
vals ; and whiskey was ordered to be given according to circumstances. Hot-water 
cans, properly wrapped, were applied along the legs, and the cotton jacket to the 
chest continued. 
On the 19th a deep red flush appeared upon the left cheek and spread gradually, 
until it involved forehead and eyelids and the margin of the nose. As there were 
several cases of erysipelas in the wards, there was no doubt as to the meaning of 
this. Strange to say, however, the temperature was not markedly influenced, 
varying between 97° and 99°, and continuing for the most part at about 97.6°, 
until the 24th, when the local manifestations of the erysipelatous process reached 
their height coincidentally with the development of a new area of consolidation in 
the left lung, which gave the characteristic percussion and auscultation signs of a 
basal lobar pneumonia. The local conditions in the right lung had been gradually 
ameliorating ; these shortly became worse. On the 25th the patient had a tem- 
perature of 100°; respirations 52 ; pulse 76. Ten drops of tincture of chloride 
of iron was then given every three hours, and an ointment of ichthyol applied to 
the face. Atropine was increased to of a grain, and strychnine to Ag of a 
grain. In place of the ammonium carbonate, half a fluid drachm of the aromatic THERAPEUTIC USES OP THE NITRITES. 
5 
spirits of ammonia was given every half hour, in one-half ounce of whiskey ; and 
twenty drops of the fluid extract of coca was given every hour at a later period. 
The chest was actively dry cupped and counter-irritation kept up by sinapisms 
and poultices. On the 29th the temperature was, at 11.30 A. m., 96.2°; respira- 
tions 48 ; pulse 66 ; at 6 p. M., temperature 97.4°; respirations 52 ; pulse 84. 
On February 5, the morning temperature was 97°; respirations 20; pulse 80. 
On February 8, temperature was normal. Atropine, sti’ychnine, amyl nitrite, 
with alcohol according to circumstances, was now the treatment. The temperature 
continued to vary between 97° and the normal line, keeping usually below 98°, 
occasionally falling as low as 96.4°; finally, on the 29th of March, becoming and 
thereafter remaining normal. At this time the respirations were 18 and the pulse 
72. The pulse was now regular, comparatively strong, and much fuller than it 
had ever been ; alcohol had been discontinued. The patient continued steadily to 
improve in all respects, and when transferred to the Soldiers’ Home was capable 
of a greater degree of exertion without dyspnoea, than he had been for many years. 
The interest in this case, if we set aside the prolonged low 
temperature which was so common in cases of influenza, is 
almost exclusively therapeutic. The well known tendency of 
influenza to bring about death in cases of such marked cardiac 
impairment as this patient presented, led to the formulation of a 
gloomy prognosis; and the patient’s condition during the height 
of his pneumonia, and again when the smouldering embers of the 
pneumonia were relighted by the erysipelas, was such as to justify 
the gravest apprehensions. Antipyretic medication was evidently 
counter-indicated, but had any of the coal-tar compounds been 
administered for the relief of pain, as was so common, and, I 
believe, so unfortunate a practice throughout Europe and Amer- 
ica during the prevalence of the pandemic, doubtless the result 
would have been in accordance with our fears. 
Again, upon first sight, the cardiac conditions would have 
seemed to emphasize the indication for digitalis presented by the 
pneumonia. When the case came under my care, however, it 
was quite evident that digitalis had been of no avail, while the 
interpretation of the physical conditions—including among 
these the great disproportion between pulse rate and respiration 
—which seemed to me most obvious, was a direct counter-indica- 
tion to its employment. Both right ventricle and left ventricle 
were enlarged, but during the acute attack it was impossible to 
determine whether hypertrophy had kept pace with dilatation. 
The valvular conditions had largely to determine the choice of 
therapeutic agents. With the current of blood obstructed at its 
entrance into the aorta, and with an incompetent mitral valve 6 
THERAPEUTIC USES OP THE NITRITES. 
permitting regurgitation into the auricle at the moment of 
it seemed evident that the most pressing necessity was to hurry 
the cardiac rhythm, so as to diminish the time and pressure of 
mitral leakage. 
Prolongation of the diastole must have been futile so long as 
the aortic obstruction prevented the increased quantity of blood, 
which might accumulate in the ventricle during the prolonged 
diastole, from finding its way out, except backward through 
the incompetent mitral, through the auricle and pulmonary 
veins, into the pulmonic circulation; there to increase pul- 
monary congestion and, therefore, the difficulty of breathing. 
It is true that a strengthening of the muscular contraction, within 
limits, was also of prime importance; but the considerations just 
mentioned indicated that digitalis was not the proper agent by 
which to secure this strength, while its effect in heightening sys- 
temic blood pressure was an additional reason against its use. 
Atropine and strychnine were therefore chosen, while nitrite of 
amyl was given in order to diminish the load placed upon the 
heart, by lowering the blood pressure; in this way partially com- 
pensating for aortic obstruction. Amyl nitrite was chosen in 
preference to other nitrites by reason of the greater rapidity 
and greater fugacity of its effect; thus permitting a better 
control. Its internal use is new in this country, though long 
practiced in England by B. W. Richardson. 
The result of treatment in this case seems to have proved the 
correctness of the theories upon which it was based. 
Extraordinary tolerance of nitrites is occasionally encountered, 
but I have never met with a case so rebellious to their influence 
as the case of angina here reported; nor, on the other hand, have 
I ever seen a more striking manifestation of their power for 
relief of this condition when once the proper dosage had been 
reached. Attention should also be called to the hypodermatic 
method of administration, which, if carefully conducted, involves 
little risk of local trouble. 
These two cases illustrate very well the applicability of the 
nitrites to two methods of restoring equilibrium of circulation. 
As the proper balance of function constitutes health, the aim of 
the therapeutist must be to re-establish that balance in the most 
feasible manner, and with the least alteration of functions other THERAPEUTIC USES OF THE NITRITES. 
7 
than those implicated in the existing disturbance. Broadly speak- 
ing, he must choose between two methods : first, the direct method, 
that of elevating a depressed function, or depressing an unduly 
exalted function, to the normal level; second, the indirect method, 
that of depressing or elevating a normal function, to the abnormal 
level of a disturbed function with which it may be correllated. 
As the first case illustrates the direct method, depression of 
abnormally exalted function; so the second case illustrates the 
indirect method, compensatory depression of normal function. 
It is to the insistence of Bartholow upon the utility of lowering 
peripheral arterial tension by the use of the nitrites in cases of 
impaired cardiac vigor, that the medical profession in America 
owes the knowledge which gives power to accomplish results that 
to the lay observer seem hardly short of miraculous.