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Observations concerning the effects of blood upon the action of a digitalis glycoside
79b
AMERICAN
HEART
JOURNAI.
by inference, the solar, together contributed little to the total conditions of the study, being less than 5 per cent of the total. Schlichter, Objective 1948.
J. G., Wilburne, Determination
M., and Grossman, of Circulation Time
M.: The in Man.
insensible
water
loss under
the
DURAFI.
Use of Acetylcholine Am. J. M. SC. 216523
in tht: (Nov.),
In the course of a study of the effects of acetylcholinr, it was noted that an accurate objective determination of the circulation time in unanesthetized normal dogs and anesthetized open-chestetl animals may be obtained by the use of this substance. The circulation time obtained with this substance is shorter, shows fewer variations, and appears superior to most methods applicable to animals. One distinct advantage is that an llnequivocal end point can be determined electrf, cardiographically. The results indicated that acetylcholine also offers a clear end point for the objective determination of circulation time in man. The doses used caused varying degrees of sinus slowing or .isystole. The minimal dose evoking such response varied in the different patients, but the average was 40 milligrams. Inasmuch as doses of more than 60 mg. were not administered, failure to obtain a circulation time measurement in some patients may have been due to inadequate, doses. The action of the drug on the heart, on the basis of animal experiments, appears to be a direct one whereby the acetylcholine passes via the coronary vessels to the sinus node and the -1-V junction. A correlation of the circulation time with other clinical and laboratorv finding5 has shown that the normal circulation time varies between 1.2 and 6 seconds. A circulaticjn lime over 7 seconds was found to be definitely abnormal. Compared with other methods, acetylc,holinc yields a distinctly shorter circulation time. The small volume and the short duration of the injection reduces the range of variation seen with the sodium cyanide, thiamine, and Diodract mrthods.
The onl), serious objection to the use of this test for the determination of the circulation time in man is the induction of multiple premature systoles and auricular fibrillation. The latter was observed in two cases. Roth of these patients had hypertension and coronary sclerosis and one \vas also markedly anemic. The margin of safety may be very small. In one case, 20 mg. had no effect whereas 25 mg. produced asytole followed by auricular fibrillation. In both cases in which auricular fbrillation occurred the mechanism was broken and sinus rhythm re-established b\the administration of oral quinidine. Atropine injections and oxygen inhalation did not abolish the arrhythmia. It is concluded that while acetylcholine may be used for simple, accurate, and objective measurements of rirculation time in man, it cannot be regarded as an innocuous proDURAST. cedure for the patient. Rine,
R., the
Jr., Action
and Friedman, of a Digitalis
M.: Observations Glyeoside. i\m.
Concerning J. M. SC. 216534
the Effects of Rlood (Nov.), 1948.
Upon
In a previous study, it was found possible, by means of the embryonic duck heart preparation, to detect as little as 0.05 microgram of a digitalis glycoside per cubic centimeter of Tyrode’% solution. The extreme sensitivity of this preparation to glycoside in Tyrode’s solution suggested the possibility that perhaps minute amounts might be detected in blood also. In order to stantlardize this type of detection, however, it was thought necessary to determine separately thr effects of blood cells and serum of whole blood. It \vas found that rat and human blood sera inhibited markedly the effect of the glycosidc. This retardation of action, however, was not marked at moderate concentration of the glycosidc (1.0 microgram per cubic centimeter), but only at low concentrations (below 1.0 microgram pet cubic centimeter). It is suggested that the retardation in serum is not due primarily to the action of the serum on the drug, but rather to the inability of the embryonic heart to respond quickly to .a medium low in ionized calcium (about 5.0 mg. per 100 c.c.). It was of particular interest, hoa ever, that as little as 0.1 microgram of glycoside in 1.0 C.C. of human serum could be detected b!, means of the preparation. Perhaps even more important was the finding that the time of OCW-rence of the “digitalis effect” depended upon the concentration of the glycoside in the serunl. ‘L‘his last finding allows the possibility of malting quantitative assays of the content in any given serum sample suspected of containing it. DURANT.
AMERICAN
HEART
JOURNAI.
by inference, the solar, together contributed little to the total conditions of the study, being less than 5 per cent of the total. Schlichter, Objective 1948.
J. G., Wilburne, Determination
M., and Grossman, of Circulation Time
M.: The in Man.
insensible
water
loss under
the
DURAFI.
Use of Acetylcholine Am. J. M. SC. 216523
in tht: (Nov.),
In the course of a study of the effects of acetylcholinr, it was noted that an accurate objective determination of the circulation time in unanesthetized normal dogs and anesthetized open-chestetl animals may be obtained by the use of this substance. The circulation time obtained with this substance is shorter, shows fewer variations, and appears superior to most methods applicable to animals. One distinct advantage is that an llnequivocal end point can be determined electrf, cardiographically. The results indicated that acetylcholine also offers a clear end point for the objective determination of circulation time in man. The doses used caused varying degrees of sinus slowing or .isystole. The minimal dose evoking such response varied in the different patients, but the average was 40 milligrams. Inasmuch as doses of more than 60 mg. were not administered, failure to obtain a circulation time measurement in some patients may have been due to inadequate, doses. The action of the drug on the heart, on the basis of animal experiments, appears to be a direct one whereby the acetylcholine passes via the coronary vessels to the sinus node and the -1-V junction. A correlation of the circulation time with other clinical and laboratorv finding5 has shown that the normal circulation time varies between 1.2 and 6 seconds. A circulaticjn lime over 7 seconds was found to be definitely abnormal. Compared with other methods, acetylc,holinc yields a distinctly shorter circulation time. The small volume and the short duration of the injection reduces the range of variation seen with the sodium cyanide, thiamine, and Diodract mrthods.
The onl), serious objection to the use of this test for the determination of the circulation time in man is the induction of multiple premature systoles and auricular fibrillation. The latter was observed in two cases. Roth of these patients had hypertension and coronary sclerosis and one \vas also markedly anemic. The margin of safety may be very small. In one case, 20 mg. had no effect whereas 25 mg. produced asytole followed by auricular fibrillation. In both cases in which auricular fbrillation occurred the mechanism was broken and sinus rhythm re-established b\the administration of oral quinidine. Atropine injections and oxygen inhalation did not abolish the arrhythmia. It is concluded that while acetylcholine may be used for simple, accurate, and objective measurements of rirculation time in man, it cannot be regarded as an innocuous proDURAST. cedure for the patient. Rine,
R., the
Jr., Action
and Friedman, of a Digitalis
M.: Observations Glyeoside. i\m.
Concerning J. M. SC. 216534
the Effects of Rlood (Nov.), 1948.
Upon
In a previous study, it was found possible, by means of the embryonic duck heart preparation, to detect as little as 0.05 microgram of a digitalis glycoside per cubic centimeter of Tyrode’% solution. The extreme sensitivity of this preparation to glycoside in Tyrode’s solution suggested the possibility that perhaps minute amounts might be detected in blood also. In order to stantlardize this type of detection, however, it was thought necessary to determine separately thr effects of blood cells and serum of whole blood. It \vas found that rat and human blood sera inhibited markedly the effect of the glycosidc. This retardation of action, however, was not marked at moderate concentration of the glycosidc (1.0 microgram per cubic centimeter), but only at low concentrations (below 1.0 microgram pet cubic centimeter). It is suggested that the retardation in serum is not due primarily to the action of the serum on the drug, but rather to the inability of the embryonic heart to respond quickly to .a medium low in ionized calcium (about 5.0 mg. per 100 c.c.). It was of particular interest, hoa ever, that as little as 0.1 microgram of glycoside in 1.0 C.C. of human serum could be detected b!, means of the preparation. Perhaps even more important was the finding that the time of OCW-rence of the “digitalis effect” depended upon the concentration of the glycoside in the serunl. ‘L‘his last finding allows the possibility of malting quantitative assays of the content in any given serum sample suspected of containing it. DURANT.