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The effect of aminophylline on the prothrombin time in man
SELECTED
549
ABSTRACTS
increased the heart rate by about 20 per cent. The possibility that an aortic reflex or increased respiratory movements were responsible for the cardiac acceleration during the infusion was excluded by the fact that the blood pressure change was very slight and that no significant change in respiratory rate was noted. In the case of the arteriovenous fistula, closure of the fistula produced an initial increase of 30 mm. in the arterial pressure, but the pressure fell promptlyto its original level in spite of the The venous pressure, on the other hand, decreased to 25 mm. of water fistula remaining closed. below its initial level and this hypotension persisted. The heart rate decreased from 100 to 60 beats per minute and then maintained a constant rate of 75. The association of the slower heart rate and lower venous pressure in the presence of a relatively unchanged arterial pressure was considered further evidence of the existence of the Rainbridge reflex. The administration of 1.5 mg. of atropine completely suppressed the response of the heart to compression of the tistula. Acceleration of the respiratory rate by over 10 per cent occurred during the infusion of serum in eight of the eleven cases. On the other hand, altering the venous pressure by compressing and opening the fistula did not change the respiratory rate. When the venous pressure was elevated by infusion in the four subjects who received atropine, there was no increase in the respirator?, rate. This respiratory reaction as it occurs in man is considered comparable to that described in the dog but is inconstant. The Bainbridge reflex is concluded to be an important but partial element in determining exercise tachycardia. L.&PLACE. Goldfinger,
Am.J.M.Sc.
D.,
and
212:418
Wosika,
(Oct.),
P.
H.:
The
Electrocardiographic
Effects
of
Prostigmine.
1946.
The fact that tachycardia remains a difficult problem therapeutically and often interferes with the proper evaluation of the myocardial status through the interpretation of the electrocardiogram led the authors to study the effects of prostigmine. The study was felt to be especially indicated because of recent reports extolling the effect of this medication in all forms of tachycardia. The electrocardiographic changes were therefore observed in forty-two patients to whom 1 mg. of prostigmine methylsulfate was administered subcutaneously. The cardiac rate was slowed in 86 per cent of the patients studied. The series included patients with both organic and functional conditions. While this slowing may have been as little as IO beats per minute in some instances, yet a similar result could not be obtained by any other method. Besides a decreased rate, other effects were noted, including transient inversion of the P wave, increase in amplitude of the QRS, increase in the amplitude of the T waves, separation of the fused T and P wave in auriculoventricular block, and slowing of the ventricular rate in auricular fibrillation and Most of the effects upon the form of the electrocardiogram were explained upon am-icular flutter. the basis that the rate is slowed by stimulation of the parasympathetics. The P-R interval was uninfluenced except in one case of neurocirculatory asthenia in which it was shortened from 0.18 to 0.16 second and in one case of rheumatic heart disease in which it was lengthened from 0.16 to 0.18 second. The effect of the oral preparation of prostigmine bromide was disappointing when used therapeutically, notable slowing being achieved only with doses which produced intolerable side effects. The procedure recommended in the study of the electrocardiogram is the comparison of the complete electrodardiogram before and twenty minutes after the injection. I~JRANT.
Breytspraak, thrombin
R. W., Time
The and Greenspan, F. S.: in Man. Am.J.M.Sc. 212:476
Effect
of
(Oct.),
1946.
Aminophylline
on
the
Pro-
Aminophylline was administered orally and intravenously, in full dosage, to a small series of young adult, male patients with mild bronchial asthma. The effects of the drug were studied with respect to the changes in the dilute (12.5 per cent) plasma prothrombin time. No significant
550
AMERICAN
hyperprothrombinemia vious observations, by these previous
HEART
could be demonstrated and would seem to indicate studies is unwarranted.
JOURNAL
in any of these cases. This that fear of increased clotting
is in contrast to pretendencies suggested DURANT.
Priest,
W.
S.,
Penicillin
New
Smith,
J.
Therapy
England
M., and
J. Med.
and the
235:699
McGee,
C.
Pathologic
(Nov.
14),
J.:
The
Lesion
of
Effect
of Anticoagulants
Subacute
Bacterial
on
the
Endocarditis.
1946.
Thirty-four patients with subacute bacterial endocarditis were treated with penicillin. Twelve of these received either heparin or dicumarol or both from the outset of penicillin therapy, three received anticoagulants with the penicillin only in the last of several courses of therapy, and nineteen were treated without anticoagulants. Difficulty was experienced in maintaining the desired coagulation time when heparin was administered, and in maintaining the desired proConsiderable variation in individual response was observed with thrombin time after dicumarol. both drugs. In three patients, embolic phenomena disappeared after anticoagulants were given, but in five, embolism first appeared during their administration, and two additional patients suffered massive, fatal hemorrhages while receiving anticoagulants. This complication was not Of the fifteen patients to whom anticoagulants observed in any of the nineteen control cases. Howwere given, eight died; whereas of the nineteen treated with penicillin alone only five died. ever, the doses of penicillin given were not uniform, and the incidence of recovery was related to the size of daily penicillin dosage regardless of whether or not anticoagulants were given. Histologically no conclusive evidence in favor of anticoagulants collld be demonstrated. The amount of fresh fibrin present on the valvular lesions was not demonstrably less than in untreated patients. The authors conclude that no evidence was found that anticoagulants to penicillin therapy in the treatment of subacute bacterial endocarditis.
are a necessary
adjunct KAY.
Holman,
E. : Arteriovenous
Boentgenologic Fistula
Kymographic and
Their
Studies Interpretation.
of
the
Ann.
Heart
Surg.
in
the
124:920
Presence
(Nov.),
of
an
1946.
Roentgenologic kymography provides important observations on the effect upon the heart and large vessels of closing a large arteriovenous fistula. The immediate effect is shown to be This distention is due to backing additional distention of an already dilated heart and aorta. up into the arterial bed of the blood formerly flowing through the fistula into the capacious venous bed. Since a large fistula of long duration is invariably accompanied by an increased total blood volume, the entire arterial bed, including the left heart and the aorta, is overdistended by this increased blood volume when the leak into the venous bed is suddenly closed. The immediate effect of sllch an overdistention of the arterial tree is a marked elevation of the systemic blood pressure, which is promptly though not completely rectified by a slowing of the cardiac contractions. This mechanism is dependent upon stimulation of the fibers of the depressor nerve in the arch of the aorta by the overdistention of this vessel which follows closure of the fistula and which is dependent upon the increase in total blood volume that occurs in the presence of a fistula of large size and long duration. The response is eliminated by atropinization of the patient and is therefore considered to be vagal in origin. If the fistula is closed permanently by operation, the blood pressure and heart rate return to normal through the gradual reduction of blood volume to normal. That the increase in blood volume and resulting circulatory effects occurs in all fistulas to greater or less degree seems likely, but these changes and effects are not always demonstrable by present instruments of precision or by present scientific methods in small fistulas with small increases in blood volume. In small fistulas also, these changes may be masked by other physiologic adjustments such as peripheral vasodilatation which may obviate the increase in general blood pressure when the blood volume increase is small. NAIDE.
549
ABSTRACTS
increased the heart rate by about 20 per cent. The possibility that an aortic reflex or increased respiratory movements were responsible for the cardiac acceleration during the infusion was excluded by the fact that the blood pressure change was very slight and that no significant change in respiratory rate was noted. In the case of the arteriovenous fistula, closure of the fistula produced an initial increase of 30 mm. in the arterial pressure, but the pressure fell promptlyto its original level in spite of the The venous pressure, on the other hand, decreased to 25 mm. of water fistula remaining closed. below its initial level and this hypotension persisted. The heart rate decreased from 100 to 60 beats per minute and then maintained a constant rate of 75. The association of the slower heart rate and lower venous pressure in the presence of a relatively unchanged arterial pressure was considered further evidence of the existence of the Rainbridge reflex. The administration of 1.5 mg. of atropine completely suppressed the response of the heart to compression of the tistula. Acceleration of the respiratory rate by over 10 per cent occurred during the infusion of serum in eight of the eleven cases. On the other hand, altering the venous pressure by compressing and opening the fistula did not change the respiratory rate. When the venous pressure was elevated by infusion in the four subjects who received atropine, there was no increase in the respirator?, rate. This respiratory reaction as it occurs in man is considered comparable to that described in the dog but is inconstant. The Bainbridge reflex is concluded to be an important but partial element in determining exercise tachycardia. L.&PLACE. Goldfinger,
Am.J.M.Sc.
D.,
and
212:418
Wosika,
(Oct.),
P.
H.:
The
Electrocardiographic
Effects
of
Prostigmine.
1946.
The fact that tachycardia remains a difficult problem therapeutically and often interferes with the proper evaluation of the myocardial status through the interpretation of the electrocardiogram led the authors to study the effects of prostigmine. The study was felt to be especially indicated because of recent reports extolling the effect of this medication in all forms of tachycardia. The electrocardiographic changes were therefore observed in forty-two patients to whom 1 mg. of prostigmine methylsulfate was administered subcutaneously. The cardiac rate was slowed in 86 per cent of the patients studied. The series included patients with both organic and functional conditions. While this slowing may have been as little as IO beats per minute in some instances, yet a similar result could not be obtained by any other method. Besides a decreased rate, other effects were noted, including transient inversion of the P wave, increase in amplitude of the QRS, increase in the amplitude of the T waves, separation of the fused T and P wave in auriculoventricular block, and slowing of the ventricular rate in auricular fibrillation and Most of the effects upon the form of the electrocardiogram were explained upon am-icular flutter. the basis that the rate is slowed by stimulation of the parasympathetics. The P-R interval was uninfluenced except in one case of neurocirculatory asthenia in which it was shortened from 0.18 to 0.16 second and in one case of rheumatic heart disease in which it was lengthened from 0.16 to 0.18 second. The effect of the oral preparation of prostigmine bromide was disappointing when used therapeutically, notable slowing being achieved only with doses which produced intolerable side effects. The procedure recommended in the study of the electrocardiogram is the comparison of the complete electrodardiogram before and twenty minutes after the injection. I~JRANT.
Breytspraak, thrombin
R. W., Time
The and Greenspan, F. S.: in Man. Am.J.M.Sc. 212:476
Effect
of
(Oct.),
1946.
Aminophylline
on
the
Pro-
Aminophylline was administered orally and intravenously, in full dosage, to a small series of young adult, male patients with mild bronchial asthma. The effects of the drug were studied with respect to the changes in the dilute (12.5 per cent) plasma prothrombin time. No significant
550
AMERICAN
hyperprothrombinemia vious observations, by these previous
HEART
could be demonstrated and would seem to indicate studies is unwarranted.
JOURNAL
in any of these cases. This that fear of increased clotting
is in contrast to pretendencies suggested DURANT.
Priest,
W.
S.,
Penicillin
New
Smith,
J.
Therapy
England
M., and
J. Med.
and the
235:699
McGee,
C.
Pathologic
(Nov.
14),
J.:
The
Lesion
of
Effect
of Anticoagulants
Subacute
Bacterial
on
the
Endocarditis.
1946.
Thirty-four patients with subacute bacterial endocarditis were treated with penicillin. Twelve of these received either heparin or dicumarol or both from the outset of penicillin therapy, three received anticoagulants with the penicillin only in the last of several courses of therapy, and nineteen were treated without anticoagulants. Difficulty was experienced in maintaining the desired coagulation time when heparin was administered, and in maintaining the desired proConsiderable variation in individual response was observed with thrombin time after dicumarol. both drugs. In three patients, embolic phenomena disappeared after anticoagulants were given, but in five, embolism first appeared during their administration, and two additional patients suffered massive, fatal hemorrhages while receiving anticoagulants. This complication was not Of the fifteen patients to whom anticoagulants observed in any of the nineteen control cases. Howwere given, eight died; whereas of the nineteen treated with penicillin alone only five died. ever, the doses of penicillin given were not uniform, and the incidence of recovery was related to the size of daily penicillin dosage regardless of whether or not anticoagulants were given. Histologically no conclusive evidence in favor of anticoagulants collld be demonstrated. The amount of fresh fibrin present on the valvular lesions was not demonstrably less than in untreated patients. The authors conclude that no evidence was found that anticoagulants to penicillin therapy in the treatment of subacute bacterial endocarditis.
are a necessary
adjunct KAY.
Holman,
E. : Arteriovenous
Boentgenologic Fistula
Kymographic and
Their
Studies Interpretation.
of
the
Ann.
Heart
Surg.
in
the
124:920
Presence
(Nov.),
of
an
1946.
Roentgenologic kymography provides important observations on the effect upon the heart and large vessels of closing a large arteriovenous fistula. The immediate effect is shown to be This distention is due to backing additional distention of an already dilated heart and aorta. up into the arterial bed of the blood formerly flowing through the fistula into the capacious venous bed. Since a large fistula of long duration is invariably accompanied by an increased total blood volume, the entire arterial bed, including the left heart and the aorta, is overdistended by this increased blood volume when the leak into the venous bed is suddenly closed. The immediate effect of sllch an overdistention of the arterial tree is a marked elevation of the systemic blood pressure, which is promptly though not completely rectified by a slowing of the cardiac contractions. This mechanism is dependent upon stimulation of the fibers of the depressor nerve in the arch of the aorta by the overdistention of this vessel which follows closure of the fistula and which is dependent upon the increase in total blood volume that occurs in the presence of a fistula of large size and long duration. The response is eliminated by atropinization of the patient and is therefore considered to be vagal in origin. If the fistula is closed permanently by operation, the blood pressure and heart rate return to normal through the gradual reduction of blood volume to normal. That the increase in blood volume and resulting circulatory effects occurs in all fistulas to greater or less degree seems likely, but these changes and effects are not always demonstrable by present instruments of precision or by present scientific methods in small fistulas with small increases in blood volume. In small fistulas also, these changes may be masked by other physiologic adjustments such as peripheral vasodilatation which may obviate the increase in general blood pressure when the blood volume increase is small. NAIDE.