A CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN1

HAROLD C. BAILEY

From the Pharmacological Laboratory of Cornell University Medical College

Received for publication, August 3, 1909.

Strophanthus has a reputation as a heart stimulant second only

to that of digitalis, but the variable clinical results obtained have
been the cause of much discussion.
Until recently it has been used by the mouth almost exclusively in
therapeutics but when employed by intravenous injection the results
have been more nearly in accord with its pharmacologic action. Ex-
periments still in progress in this laboratory seem to show that the
absorption from the gastro-intestinal tract is very uncertain.2
Fraenkel and Schwartz3 in 1907 published the results of the intra-
venous injection of amorphous strophanthin. Consideriig the dose
used (usually one milligram, Boehringer and Son’s) and the infrequent
epetition their results were remarkable.
About a year later Danielopulo4 reported twenty-three cases in
which he used Merck’s amorphous strophanthin repeating the dose
for two or three days as required but never giving more than one milli-
gram in twenty-four hours. He decided that it should be classed as
one of the best heart tonics because of its quick and energetic action.
A number of other observers have obtained similar results.
Hewlett5 in 1908 reported a case in which he believed strophanthin
caused intra-ventricular heart-block.
Crystalline strophanthin which Thorns obtained from Strophanthus

‘Read before the New York Academy of Medicine, section on Medicine, May 18,
1909.
2 R. A. Hatcher: Amer. Journ. of Physiol., vol. xxiii, no. iv, 1909.

#{176}Fraenkel and Schwartz, Archiv f#{252}r

Exper. Path. und Pharmacologie, vol. lvii,
p. 79, 1907.
Danielopoulo: Archiv. de Ma] de Cour., Nov., 1908.
l Hewlett: Archiv. of Int. Med., Sept., 1908.
44

350 HAROLD C. BAILEY

gratus, and which is said to be identical with ouabain, acts qualita-

tively like the amorphous strophanthin, over which it has the advan-
tage of being a perfectly definite substance with well-defined solu-
hilitics and melting point. It is also more than twice as active as the
amorphous strophanthins, as 0.4 mg. of the crystalline strophanthin is
approximately equivalent to 1 mg. of the amorphous.6
After an extensive study of its toxic action on animals in the labora-
tory it was investigated clinically in Bellevue Hospital and the results
of these investigations form the subject of this paper.
The crystalline strophanthin was dissolved in 4000 times its weight
of normal saline which was then sterilized by boiling and placed in
serum tubes which were sealed in the flame.
In the first series of twenty cases running from February to June,
1908, with three exceptions, daily doses of from three-tenths to five-
tenths of a milligram were given by deep muscular injection usually
into the buttock, the medication in many instances extending over a
period of several days.
All eases in this group showed signs of loss of compensation and were
patients to whom digitalis would have been given ordinarily.
It was found that a daily dose of one-half milligram of crystalline
strophanthin caused some general improvement in the pulse, a lessen-
ing of dyspncea and at times some increase in the amount of urine.
Sphygmographic tracings were not taken in these eases and the results
in most instances were not at all striking. I did not feel convinced
that the results obtained were not due, in part at least, to rest in bed,
freedom from work and worry and to hospital regimen.
Two cases are worthy of detailed description.
Case 1. The patient, a well-developed man of 27, was admitted
to the service of Dr. Thompson, April 9, 1908. lIe was suffering from
marked dyspncea, cyanosis and general anasarca. There were double
aortic and mitral murmurs and the heart was dilated. The urine
contained albumen and casts. He received two injections of one-half
milligram each in forty-eight hours. The dyspna disappeared and
the pulse improved but the edema remained unchanged. He refused
further intramuscular medication and was given five milligrams of

6 Hatcher and Bailey: Journ. Amer. Med. Assn. vol. lii, pp. 5-9, 1909.
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 351

crystalline strophanthin by mouth, receiving two doses in forty-eight

hours. His symptoms remained unchanged and the strophanthin
treatment was discontinued. He died seven days later and autopsy
showed aortic, mitral and tricuspid lesions accompanied by a chronic
nephritis.
The dose of strophanthin that this patient received by the mouth,
five milligrams, was equivalent in toxicity to twelve milligrams of the
official strophanthin or about thirty-six times the single dose advised
by the Pharmacopaia. This amount continued for two days had no
apparent effect.
Case 2. The patient, a female, aged 65, was admitted to the service
of Dr. Dana, June 3, 1908, and was discharged June 17. She gave a
history of rheumatism and regular indulgence in moderate amounts
of alcohol. Two months before admission she had had an attack
of dyspncia, palpitation and vertigo. Since then similar attacks had
occurred after exertion, and at the time of her admission these symp-
toms were marked and were accompanied by slight edema of the ex-
tremities. Her heart was enlarged, the sounds were feeble amid ill
defined, and the rate was estimated to be 200. Duringthefirsttwenty-
four hours she was given a cathartic and two doses of morphin sulphate
of one-fourth grain each with ten minims of the tincture of belladonna.
On the following day her condition had not improved. The heart
rate was about 200 and the blood pressure 190. Half a milligram of
crystalline strophanthin was given by intramuscular injection. Six
hours later the heart rate was 88, and in twelve hours it was reduced
to 70. The blood pressure was 180 and the dyspna and other
symptoms had disappeared. No further medication was given during
her stay in the hospital and during this time the heart rate varied
between 80 and 90.
In our second series there is a similar case of interstitial myocarditis
which was not affected to such an extent by one dose.
Owing to the want of entirely satisfactory results in the first series
of experiments it was decided to increase the dose somewhat when
necessary in the second series, and the further question of dosage will
be considered at the end of this paper.
There were twenty-seven cases in the second series extending from
October, 1908, to March, 1909. They are classified as follows: four
352 HAROLD C. BAILEY

cases of mitral disease, eight of mitral and tricuspid disease, four cases
of aortic regurgitation, five of interstitial myocarditis with valvular
lesions, three with interstitial myocarditis without valvular lesions,
three with valvular disease accompanied by marked nephritis. With
six exceptions these patients had an extreme degree of cardiac insuffi-
ciency with marked dilatation. The medication was controlled by the
study of tracings made by a Jacquet sphygmocardiograph and with
numerous blood pressure readings from a Stanton apparatus.
The description of the first two cases shows approximately the in-
terval before the effects follow an intravenous injection of strophanthin
and also the approximate duration of a single dose.
Case 14. A motorman, aged 41, was admitted to the service of
Dr. Dana, September 24, 1908, and was discharged, February 3, 1909.
lIe gave a history of rheumatism and had, when admitted, a dilated
heart with a systolic mitral and a systolic tricuspid murmur. There
was also considerable effusion in the pericarclial sac. He was placed
on digitalis and improved steadily. On November 16 the medication
was discontinued and he was allowed to walk about the ward. On
December 2 his pulse became rapid and irregular and he had a feeling
of distress over the precordium. A tracing was taken at noon.

451 ,p

TRACING I, NO. 14, 12/2/08, 11:45 AM. JUGULAR (UPPER) AND RADIAL TRACINGS.
RATE 111, IRREGULAR RHYTHM DUE TO EXTRA SYSTOLES AND SERIES OF EXTRA

SYSTOLES. JUGULAR TRACING SHOWS TRICUSPID REGURGITATION.

The rate was 111 with great irregularity and the jugular tracing
showed tricuspid regurgitation. Half a milligram of crystalline stro-
phanthin was given by vein and one hour later the irregularity had
almost disappeared and the rate was 78.
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 353

7F. /3i#{176}/3o

TRACING 2, NO. 14, 12/2/08, 1:20 P.M. ONE HOUR AFTER INJECTION. RATE 78.
CHANGE IN RHYTHM. ABSENCE OF SERIES OF EXTRA SYSTOLES.

?a 4.c. 5’ O

TRACING 3, NO. 14, 12/2/08, 4:20 P.M. FOUR HOURS AFTER INJECTION. RATE 84
EXTRA SYSTOLES OCCASIONALLY PRESENT.

The effect was maximal before the end of four hours, and in twelve
hours it had commenced to wane.
At the end of twenty-four hours the condition was about the same
as before the dose was given. The systolic blood pressure was 130 and
did not vary more than three millimeters throughout the experiment.
This patient received strophanthin for one or two days and was then
placed on digitalis.
C’ase 16’. A well developed male, aged 27, was admitted to the ser-
vice of Dr. Coleman, December 12,, 1908. He gave no history of
rheumatism. Two years before admission he had noticed that exer-
tion caused discomfort and dyspnoa. Six months later, after a march
of some miles he became exhausted, expectorated blood tinged sputum
and suffered from marked dyspncea. He was removed to his home and
after remaining in bed for some time his condition improved. Eighteen
months later he again lost compensation and after one month’s treat-
ment at home he was brought to the hospital. He was markedly
dyspnoeic and cyanotic hut had little edema. On examination double
354 HAROLD C. BAILEY

murmurs were heard at mitral, aortic and tricuspid areas. There

were thrills present at the apex and at the lower end of the sternum.
The left border of the heart was fifteen centimeters from midsternum
in the sixth space and the right border was four centimeters in the
third space. Jugular and liver pulsations were marked. The blood
pressure was 145, the pulse was 108 and very irregular.

D /2/ /g ,0

Cs2IA /6

TRACING 4, NO. 16, 12/12/08, 5 P.M. VERY IRREGULAR RHTHYM. GROUPS OF EXTRA

SYSTOLES. JUGULAR TRACING SHOWS TRICUSPID REGURGITATION. RATE 108.

A few r#{225}les
were present at the bases of the lungs and the liver
extended two centimeters below the free border of the ribs. Crystal-
line strophanthin was given by vein at 5 p.m. on the day of admission
and as no improvement had occurred at midnight the dose was repeated.
At 11 a.m. the following day the pulse was very slow and irregular.
A premature or early extra-systolic occurred with some regularity for
a short period and was followed by a very irregular period where two
or more early extra systoles would occur alternating with a few beats
of regular rhythm. -

/6 0 //#{149}/C) am’ S/ Jo L5’ic 150

TRACING 5, NO. 16, 12/13/08, 11:10 AM. EIGHTEEN HOURS AFTER PRECEDING TRAC-

ING. RADIAL PULSE WAS 30, BUT AN APEX TRACING SHOWS A PREMATURE SYS-

TOLE FOLLOWING EACH FUNDAMENTAL BEAT.

The cyanosis had disappeared and the dyspnoea was slight. The
blood pressure was 150. Because of the pronounced effect, no medica-
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 355

tion was given for twenty-four hours. At the end of that time the
effect had worn off and the patient was returning to his former con-
dition. -

The blood pressure had dropped to 130, and the pulse was, 99 and
very irregular.

Df2/,s- ‘,‘a4 /rz, 517 sr ho

4/(’,

TRACING 6, NO. 16, 12/14/08, 11:45 AM. THIRTY HOURS AFTER LAST STROPHANTHIN
INJECTION. HEART HAS RETURNED TO ITS FORMER CONDITION. UPPER TRACING
JUGULAR, LOWER RADIAL.

/0 Pk. / I-9 A

TRACING 7, NO. 16, 12/14/08, 4:10 P.M. FIVE HOURS LATER THAN THE PRECEDING.

TRACING FOUR HOURS AFTER AN INJECTION OF STROPHANTHIN. RADIAL PULSE

42, APEX BEAT 84. JUGULAR (UPPER) TRACING SHOWS AN AURICULAR WAVE AT

THE PROPER TIME, A DOUBLE WAVE DUE TO TRICUSPID REGURGITATION AND A

THIRD WAVE DUE TO A PREMATURE SYSTOLE OF BOTH AURICLE AND VENTRICLE.

IT IS LARGER THAN ANY OF THE OTHER WAVES IN THE VENOUS TRACING, BECAUSE
THE AURICLE IS FILLED WITH BLOOD AT THE TIME OF THE SIMULTANEOUS CON-
TRACTION OF THE AURICLE AND VENTRICLE.

Strophanthin was given by vein and four hours later the pulse was
perfectly regular and very slow with an extra-systole occurring with
each beat.
This patient became so much worse as soon as the strophanthin
treatment was interrupted that it was decided to continue it from day
to day. There were times when compensation seemed to be restored
and the pulse would be normal but the heart had no reserve force and
356 HAROLD C. BAILEY

would return to its previous condition. On December 27 he developed

pain in the apex of his left lung and many pleuritic r#{226}les
were present.
He expectorated large quantities of blood-tinged sputum and his
cyanosis and dyspncea were intense although his pulse was fairly
regular. His condition became constantly worse and he died Decem-
ber 29. Permission for an autopsy was refused by his friends.
Case 23 shows the marked improvement resulting from the use of
strophanthin in a case of mitral and tricuspid disease.
The patient, a poorly developed male aged twenty-one was admitted
to the service of Dr. Lambert on January 20, 1909. He gave no history
of an acute attack of rheumatism. He had been admitted to Bellevue
Hospital three times in the preceding five years with loss of compensa-
tion. For two weeks before he was brought to the hospital he had
had dyspncBa, cyanosis, edema and pain in the precordium and his
symptoms were increasing in severity. On examination he was found
to have considerable deformity of the chest caused by the protrusion of
the lower part of the sternum. His heart was rapid, feeble and irregu-
lar and at times three consecutive beats at the apex could not be felt
at the wrist and could not be shown there by a sphygmographic trac-
ing.
r

“.0 /07 // 80

TRACING 8, NO. 23, 1/20/09, 11:30 A.M. RAPID AND IRREGULAR PULSE. GROUPS OF

EXTRA SYSTOLES. JUGULAR (UPPER) TRACING SHOWS TRICUSPID REGURGITA-

TION. RATE 102?

‘/ ‘i aii

TRACING 9, TAKEN THE SAME HOUR AS THE PRECEDING TRACING BUT AT A FASTER
SPEED. APEX (UPPER) AND RADIAL TRACING SHOWING THAT THERE IS AN EXTRA
BEAT AT THE APEX THAT IS NOT PERCEPTIBLE AT THE WRIST
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 357

The left border of the heart was thirteen centimeters from midster-
num in the fifth space, and the right border, seven centimeters in the
third and fourth spaces. Systolic and diastolic murmurs were present
at the apex and a systolic murmur could be heard to the right of the
lower end of the sternum. Jugular and liver pulsations were marked,
many r#{226}leswere present at the bases of the lungs and there was
albumin in the urine. The pulse at the wrist was 102 and the blood
pressure shown by the Janeway apparatus was 92. Cyanosis and
dyspnca were marked and the lower extremities were very edematous.
He received strophanthin by vein during the first twenty-four hours
following admission. At the end of that period the pulse rate was
87 and every beat at the apex could be detected at the wrist.

#{231}‘2Z ‘I’-’ ii jog

“/2 / //
TRACINGS 10 AND 11, NO. 23, 1/21/09, 11:30 AM. APEX (UPPER) AND RADIAL TRAC-

INGS SHOWING THAT EACH BEAT AT THE HEART GOES THROUGH TO THE WRIST.
EXTRA SYSTOLES HAVE DISAPPEARED. RATE 87.

The blood pressure was 100, the cyanosis had almost disappeared,
the dyspnaa had diminished, the edema had lessened and he felt
comfortable. He was then placed on digitalis and continued to im-
prove. This patient left the hospital three months later.
The next two cases illustrate the result in chronic interstitial myo-
carditis with accompanying valvular disease.
Case 25. A fireman, aged 41, was admitted to the service of Dr.
Coleman, January 27, 1909, and was discharged February 18, 1909.
358 HAROLD C. BAILEY

He gave no history of rheumatism but his occupation entailed hard

labor and frequent exposure. His first loss of compensation had
occurred nine months before at which time he was treated in Bellevue
Hospital.
He was markedly cyanotic and dyspnceic but the extremities w’ere
only slightly edematous. The left border of the heart was fifteen
centimeters from midsternum in the fifth space, the right border four
centimeters in the third and fourth spaces. There were double mur-
murs at the apex and base and also a systolic murmur heard to the
right of the lower end of the sternum. He had marked liver and jug-
ular pulsations. The pulse was 120 and the blood pressure 102.
He received crystalline strophanthin and in twenty-four hours the
cyanosis and dyspncna had practically disappeared. The liver pulsa-
tion could not be felt and only slight regurgitation was shown by the
tracing His pulse was 75 and the blood pressure was 110. He was
then given digitalis by mouth and forty-eight hours after admission
no murmurs could be heard. The heart borders had receded one centi-
meter, the pulse had dropped to 66 and the blood pressure was 115.
A few days later a faint blowing systolic murmur could be heard again
at the apex. He was up in ten days and was discharged on the twenty-
second day.
Case 9. A woman of fifty was admitted to Dr. Thompson’s service
at the Presbyterian Hospital November 15, 1908, and was discharged
December 24. She had had pneumonia six months before, being
treated at the German Hospital. On admission she complained of
shortness of breath and pain over the heart region. Her heart was
dilated, the left border being 17-h centimeters from midsternum in the
fifth space, the right 4 centimeters in the third space. An undefined
murmur was heard at the apex. The liver could not be felt and there
was no positive pulsation in the jugular veins. The dyspnaa was in-
tense but there was no cyanosis and but moderate edema. Strophan-
thin was not given until the third day after admission at which time
she had not improved. The pulse rate at the wrist was 123 while the
apex beat was 153. The blood pressure was 150. She received crys-
talline strophanthin by deep intra-muscular injection and during the
next twenty-four hours there was marked improvement in her condi-
tion. The borders of her heart receded about one centimeter and
 #{149}‘ : - #{149} , .. - -

CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 359

most of the beats at the apex could be felt at the wrist. The stro-
phanthin was continued and at the end of forty-eight hours the apex
beat and the radial pulse rate were the same, 94, and a presystolic
murmur was heard at the apex. The dyspncea had left and the blood
pressure was 145. On the fourth day of treatment she became nau-
seated and vomited occasionally. At this time the pulse at the wrist
was 96 corresponding to 96 beats at the heart. The strophanthin was
discontinued and the patient was placed on caffein and later on digi-
talis. She was up in about fourteen days and returned home in good
condition.
The next case was one of interstitial myocarditis with no valvular
lesion. Theocin was given with the strophanthin and a large amount
of urine was l)assed in the twenty-four hours with disappearance of
the edema.
Case 27. A coal heaver, aged 40, was admitted to the service of Dr.
Thompson, March 8, 1909, and discharged April 2. He had had typhoid
fever seven years before but gave no history of rheumatism. He
used alcohol to excess habitually and his occupation entailed hard
labor. Five months before admission to Bellevue Hospital he had
first lost compensation and was then treated at the City Hospital.
Four or five days before his admission his symptoms returned and were
increasing in severity. On examination he was found to be dyspnic,
markedly cyanotic and edematous, his temperature was 102 and he had
a cough with no expectoration. The left border of the heart was four-
teen centimeters from the midline in the fifth space, the right two centi-
meters in the third space. A systolic murmur was present at the
apex and the heart was rapid and irregular.
There were marked jugular and liver pulsations, and a few rMes were
present at the bases of the lungs. No albumen or casts were found
in the urine. The blood pressure was 125.
He received strophanthin during the first twenty-four hours to-
gether with twenty grains of theocin in five-grain doses. At the end
of that period the dyspnoea, cyanosis and edema had practically dis-
appeared. The diameter of the heart was diminished by one centi-
meter, the systolic murmur could no longer be heard at the apex, the
cough was less marked and the temperature was nearly normal. The
 - - *__y - ‘-.---‘.- -,-‘-,--- -p--’;’ - - -

360 HAROLD C. BAILEY

blood pressure had risen to 145 and the pulse was 96. During this
period he had passed 122 ounces of urine.
He was given strophanthin during the next twenty-four hours and
was then placed on digitalis. His improvement continued and he
was up on the tenth day.

1rAn(v

34 I14p1 )E’d ha. 1? -

TRACING 12, NO. 27, 3/8/09, 4 P.M. JUGULAR (UPPER) AND RADIAL TRACiNGS. PULSE
VERY RAPID AND IRREGULAR. HEART IN DELIRIUM CORDIS. JUGULAR TRACING

SHOWS TRICUSPID REGURGITATION.

1r7
q,#{176}, 3/p ,qaz f. ,3P’Jo

TRACING 13, NO. 27, 3/9/09, 4 P.M. TWENTY-FOUR HOURS LATER THAN PRECEDING

TRACING. RHYTHM STILL SOMEWHAT IRREGULAR DUE TO EXTRA SYSTOLES.

27 fi, Icy #{176} ,

TRACING 14, NO. 27, 3/11/09, 4:30 P.M. THREE DAYS AFTER TREATMENT WAS STARTED.

Case 24. A corpulent woman, aged 55, was admitted to the service
of Dr. Lambert, January 15, 1909. She was dyspnceic, cyanotic and
edematous. There was marked cardiac dilatation with failure of the
right heart and edema of the lungs. The positive venous pulse of
tricuspid regurgitation was present.
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 361

*2’,’
/2-#{128}&-rrc- i2 9o
TRACING 15, NO. 24, 1/16/09, 12 NOON. JUGULAR (UPPER) AND RADIAL. TRICUSPID.
REGURGITATION PRESENT.

She received strophanthin by deep intra-muscular injection. At the

end of twenty hours her radial pulse was slowed to 78 and improved
in character, but the cyanosis and edema continued to increase.
She became delirious and died at the end of twenty-four hours.

24 ‘/7 /‘3.#{176}aAit /‘i?4% 7S

TRACING 16, NO. 24, 1/17/09, 11:30 AM. RADIAL TRACING FOLLOWING DAY, FOUR

HOURS BEFORE DEATH AND ELEVEN HOURS AFTER THE LAST INJECTION. RATE 78.

Case 17. The patient, a driver by occupation aged 35, wasadmitted

to the service of Dr. Coleman on the evening of December 19, 1908.
He gave a history of rheumatism and heart disease, having had five
previous attacks of loss of compensation. For the past year he had
been practically confined to his bed.
On admission he was dyspnceic, cyanotic, and had slight edema of
the lower extremities. The heart was dilated, the left border being
fourteen centimeters from mid-sternum in the sixth space, the right
four centimeters in the third and fourth spaces. There was a double
murmur at the apex and a systolic murmur at the tricuspid area.
During the night he was given digitalis by subcutaneous injection
but showed no improvement. On the following morning his blood
pressure was 92, his pulse was very feeble and irregular and he was
evidently in a dying condition.
362 HAROLD C. BAILEY

TRACING 17, NO. 17, 12/20/08, 3 P.M. RADIAL TRACING. RATE 102.

TRACING 18, NO. 17, 12/20,/OS, 4 P.M. JUGULAR AND RADIAL. TRICUSPID REGURG-

ITATION. NODAL RHYTHM. AURICULAR WAVE LATE IN APPEARING.

He was given strophanthin and seemed to show slight improvement.

His blood pressure was 95 and his pulse varied between 78 and 90.
His orthopncea was less pronounced but his cyanosis persisted. He
died the next day.

. . . /

TRACING 19, NO. 17, 12/21/08, 11 A.M. JUGULAR (UPPER) AND RADIAL. THREE HOURS
BEFORE DEATH AND TEN HOURS AFTER LAST INJECTION. RATE 74.

In all cases of the series the urine was increased to slight extent
but no more than could be accounted for by the improvement in the
circulation. Two patients with high blood pressure received one-
fiftieth grain of nitro-glycerin every two hours during the strophanthin
 , - -- - .. - .--- . “ ‘#{149}r-- ‘ ‘ --

CLINICAL STUDY OF CRYSTALLINE STROPHANTH1N 363

treatment and both passed large quantities of urine. Danielopoulo7

and others mention the advisability of adding theobromin to the
treatment in certain cases and case 26 shows what may be accom-
pushed in some instances by giving a diuretic with the strophan-
thin.
The blood pressure in most cases was increased by a few millimeters
of mercury, only an amount corresponding to the increased output
of the heart. Whenever the systolic pressure was as low as 95 to 110
millimeters it was increased from ten to twenty millimeters. In a
few cases where marked improvement occurred there was no rise.
The size of the heart according to percussion was diminished within
twenty-four to thirty-six hours in those cases where there was marked
dilatation and many murmurs due to dilatation entirely disappeared.
The rate and rhythm were markedly affected and in two cases the
pulse became very slow and with early extra-systole, or the so-called
bigeminal action. In one case there was noticeable lengthening of the
A-C interval but otherwise no form of heart block was produced.
Many patients suffered pain after the injections into the buttocks
and in a few cases there was considerable local reaction. No abscess
occurred and it was found that if the injection was given deep into the
buttock and the area massaged for fifteen or twenty minutes practically
no pain would result. Where it did occur it began one-half hour after
the injection and lasted from one to two hours.
Most of the injections were given intra-muscularly and this method
is generally to be preferred to the intravenous, for if a drop or two of
the solution runs back, following the withdrawal of the needle from the
vein, considerable pain results.
Fraenkel and Schwartz report having seen chills follow the intraven-
ous injection of the amorphous strophanthin. One of our patients
had a chill and a temperature of 104, after an injection of the crystalline
strophanthin into the buttock and a month or so later this same patient
had a chill following the injection of one-half milligram into the vein.
Two others had chills following the injections into the muscle. We
have no means of knowing the cause of this. The solution was sterile
and aseptic precautions were taken with every injection.

7Danielopoulo: Archiv de Mal de Cour., NOV., 1908.

364 HAROLD C. BAILEY

Most of the patients were made more comfortable and were able
to obtain sleep. This was probably mainly due to the lessening of the
dyspnoea and the general improvement in the circulation, but the drug
appears to have a slight hypnotic action.
When marked dilatation was present in aortic regurgitation the
strophanthin was as efficacious as in other valvular lesions.
Strophanthin was given to three patients with chronic nephritis
accompanied by valvular disease. Except for a moderate slowing of
the pulse very little improvement was noticed.
At the time these observations were begun, no clinical studies of
crystalline strophanthin administered subcutaneously and intraven-
ously had been reported. Hochheini had reported vomiting after
about half a milligram given to a woman on three successive days
and he advised that only very small doses be used.
In the absence of other experience I was guided in part by the result
of Hochheim’s8 observation, which appears to have been rather excep-
tion.al, and in part by the relative activity of the amorphous and the
crystalline substances.
In the first series of cases the dose was limited to half a milligram
in twenty-four hours. This never occasioned vomiting even when re-
peated for several days.
Owing to the lack of striking results in the first series of cases it
was decided to increase the dose very cautiously. After each dose of
half a milligram the action on the circulation was studied with the aid
of the Stanton sphygmomanometer and the Jacquet sphygmograph.
If no effect was seen in eight hours this dose was repeated.
A careful study of every case leads to the conclusion that no toxic
symptoms except nausea and vomiting were induced.
Two patients died during the first twenty-four hours of treatment
but their condition was so extreme that this was not unexpected.
Many clinical observers have advised that the dose of the amorphous
strophanthin by vein should be limited to one milligram per day,
though the amorphous is less toxic than the crystalline as already
stated.
In all cases the crystalline strophanthin, also called gratus strophan-

‘Hochheim: Zent. f#{252}r

in Med., vol. xxvii, p. 65, 1906.
 CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 365

thin Thorns, was used. The tracings were taken with the Jacquet
instrument and the upper and lower levers were always adjusted so
as to write on the same line. The time marking is in one-fifth seconds.
Not more than one-half milligram was given at a single injection.
The following are the largest twenty-four hour doses given in each
ease:
Case 14 received one-half milligram intravenously. This case was

used chiefly for determination of the time of onset and duration of the
action of a single dose in a case where compensation had not been
entirely lost. He was discharged later.
Case 16 received a total of one milligram. It produced general im-
provement with slowing and irregularity of the pulse due to the excit-
ability of the cardiac muscle and also to marked vagus stimulation.
This patient died eighteen days later.
Case 23 received one and one-half milligrams by intravenous injec-
tion with marked improvement. He was discharged three months
later.
Case 25 was given a total of one milligram by intramuscular injec-
tion. The result was particularly striking. The dilation was so
much diminished that the murmurs could no longer be heard. He
was discharged twenty-two days later.
Case 9 received a total of one and one-half milligrams by intramus-
cular injection with marked improvement. She was discharged bout
thirty-five days later.
Case 26 received a total of one and one-half milligrams by intra-
muscular injection. A diuretic of the caffein group was given at the
same time with good result. He was discharged twenty-five days
later.
Case 24 received a total of one milligram by intramuscular injection.
Her condition was so critical that no benefit was looked for. It will
be recalled that she had marked cardiac dilatation with all the sigus of
venous engorgement including edema of the lungs. Her pulse was
slowed a few beats per minute and was stronger in character but her
general condition did not improve and she died at the end of twenty-
four hours.
Case 17 received a total of one and one-half milligrams. His con-
dition was extremely grave. The strophanthin slowed his pulse some-

j
366 HAROLD C. BAILEY

what and made it more regular, and his orthopncea was less intense.
It was deemed unwise to push the drug further and he died the follow-
ing day.
Very careful study of both these cases revealed no toxic action of
any kind on the circulation.
Quite recently Vaguez9 injected one milligram of the crystalline
strophanthin at a dose but on the other hand Chauffard’#{176} reports twoS
deaths occurring after intravenous injection of half a milligram of the
same substance and declared he would not use it again. In one ease
he saw nausea, vomiting and localized convulsions followed by death
in one hour and a half.

CONCLUSIONS

1. While I have given the amounts just stated I wish to say most
emphatically that I do not advise that the daily dose should exceed
one-half milligram of the crystalline strophanthin, as a rule and under
no circumstances should this dose be repeated in twenty-four hours
except after careful study of the effects on the circulation.
2. Crystalline strophanthin may be given intramuscularly or in-
travenously. It should be dissolved in normal saline in the propor-
tion of 1-4000 for intramuscular injections and 1-6000 to 8000 for
intravenous.
3. Crystalline strophanthin is a valuable cardiac stimulant when
compensation is broken in chronic interstitial myocarditis or in any
form of chronic valvular disease.
4. Crystalline strophanthin should be used in this way only in
emergencies. It is not suited for continuous use and when continued
stimulation is desired, digitalis should be employed.
I wish to express my warmest appreciation to Drs. W. GilmanThomp-
son and Warren Coleman for the use of cases in their wards and for
their assistance in diagnosis and advice in treatment of these very
difficult cases.

Vaguez: Scm. Med., vol. xxix, p. 152, 1909.

10Chauffard: Sem. Med., vol. xxix, p. 167, 1909.
 ..)f.:

CLINICAL STUDY OF CRYSTALLINE STROPHANTHIN 367

Dr. R. A. Hatcher has aided me throughout this research by sug-

gestions and advice.
I am particularly indebted to Dr. L. Jaches for the excellent photo-
graphic reproductions of my tracings from which the drawings were
taken. By his care and patience he has brought out the finer de-
tails with as much clearness as exists in the originals.