Protection against cyclopropane-epinephrine induced cardiac arrhythmias by dibenamine and other agents

Special Feature Western

Society

for Clinical

Research

FIRST ANNUAL MEETING HELD IN SAN FRANCISCO NOVEMBER 7 AND 8, 1947 CHOLESTEROL METABOLISM AND ITS RELATIONSHIP TO ATHEROSCLEROSIS, CORONARY ARTERY

DISEASE,

AND ARTERIOSCLEROSIS.

Lester M. Morrison, M.D.; Lillian Hall, M.D.; and Albert L. Chancy, Ph.D., Los Angeles, California. Blood serum cholesterol and ester levels in acute coronary thrombosis have been determined in some 500 cases at the Los Angeles County General Hospital. These levels were compared to. control cases in normals and in various diseases, such as hypothyroidism, cirrhosis of the liver, nephrosis, xanthomatosis, etc. The cholesterol and ester levels were followed in coronary occlusion cases and in a normal series of controls. These cholesterol and ester levels were then followed every six weeks in the Research Clinic after the administration of 6 Gm. of choline daily. Cholesterol and ester levels were followed every six weeks in the Research Clinic-on high fat, low fat, high protein diets, and low protein diets to determine the influence of these diets on the cholesterol and ester blood levels. SUMMARY A consecutive unselected series of 200 patients with acute coronary occlusion was studied for blood cholesterol and cholesterol ester levels within forty-eight hours after hospital admission. In 68 per cent of seventy-five patients under sixty years of age with proven acute coronary occlusion hypercholesterolemia was present. In 52 per cent of 125 patients over sixty years of age with proven acute coronary occlusion a normal cholesterol level was found. CONCLUSION Coronary thrombosis age of sixty is frequently

in patients under the associated with hyper616

cholesterolemia metabolism.

and disturbances

PROTECTION

AGAINST

EPINEPHRINE

CYCLOPROPANE-

INDUCED

CARDIAC

RHYTHMIAS BY DIBENAMINE AGENTS. duced

Mark

by H.

flickerson, H.

of cholesterol

Hecht,

AR-

AND OTHER

M.D. M.D., Salt

(IntroLake

City.) After induction of anesthesia with intravenous sodium pentothal (ave. 20 mg./Kg.), dogs were maintained on a 30 per cent cyclopropane-70 per cent 02 mixture administered by endotracheal catheter with inflated cuff. After equilibration for thirty minutes, a standard challenge dose of 10 mg./Kg. epinephrine was injected intravenously in fifty seconds. Continuous standard-lead electrocardiograms were recorded during the period of epinephrine injection and until the cardiac rhythm returned to normal. Protective agents were administered ten to thirty minutes before the epinephrine. About 25 per cent of unprotected animals developed ventricular fibrillation and the remainder showed long periods of ventricular extrasystoles and ventricular tachycardia. Dibenamine (20 mg. /Kg.) almost completely eliminated all irregularities leaving a sinus tachycardia as the only response to the epinephrine. Protection was equally effective when challenge doses of 100 and 1000 mg. /Kg. were employed. Priscol (20 mg./Kg.) was only slightly less effective than dibenamine when tested with IO‘ mg./Kg. of epinephrine, but gave little protection against larger doses. Demerol (10 mg./Kg.) and large doses of atropine sulfate (1 mg. /Kg.) gave significant, but somewhat variable protection while quinidine sulfate (5. mg./Kg.), procaine hydrochloride (16 mg./Kg.) and ergotamine tartrate (0.25 mg. /Kg.) had insignificant effects. Smaller AMERICAN

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Western Society for Clinical doses of au-opine sulfate (0.1 mg./Kg.) and bilateral vagotomy did not protect, indicating that the protection afforded by massive doses of atropine is not due to its action in blocking vagal impulses. No agent was found capable of restoring normal cardiac rhythm after ventricular fibrillation was established, even when given by intracardiac injection and accompanied by cardiac massage. Dibenamine blocks most of the excitatory effects of epinephrine and sympathetic nerve impulses, but it has been shown not to sensitize animals to hemorrhagic shock. Its clinical use to prevent cardiac arrhythmias in patients under cyclopropane anesthesia is suggested.

ON THE USE OF AMMONIUM

CHLORIDE BY VEIN IN RESISTANT EDEMAAND~LIGURIA; A PRELIMINARY REPORT. Ferdinand Ripley Schemm, M.D., Great Falls, Montana.

Ammonium chloride by vein was given fiftytwo times to twenty patients in an effort to relieve edema or oliguria which had proven resistant to usual measures, 4.6 Gm. of ammonium chloride and 20 Gm. of dextrose in 1,000 cc. of distilled water appeared in vitro to give a maximum concentration of ammonium chloride without hemolysis and a maximum diuretic effect with a minimum of unpleasant reactions. The volume of the solution used was 1,000 cc. in eleven instances and 500 cc. in forty-one instances. One patient received eleven venoclyses of 500 cc. in four days. The use of ammonium chloride was limited to two classes of patients; those who were obviously near the end of a long chronic illness and on whom the immediate effect of the drug on edema was observed, and those whose critical state depended chiefly on the edema or oliguria or anuria which had resisted other measures. In twelve cases, only one of them from the hopeful class, the ammonium chloride had no effect on the edema or oliguria. Severe reactions characterized by pallor, sweating and retching, were observed in five of these twelve cases, as well as in one of the eight cases that responded. In eight cases, four from the first class and four from the second class, the ammonium chloride appeared to be solely responsible for instituting a beneficient diuresis and/or the clearing of edema. The four from the hopeful class recovered and are well or active after from one to three years. AMERICAN

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Research

The carbon dioxide combining power and plasma chlorides obtained before venoclysis failed to indicate the presence of antecedant alkalosis in those cases which responded well, or of antecedent acidosis in those which reacted badly; and any degree of acidosis that may have been induced by the venoclysis was not detectable by these determinations. It is hoped that investigations now in progress may clarify the indications for the use of ammonium chloride by vein.

STUDIES ON THE COLLATERAL CIRCULATION OF HEARTS WITH ACUTE CORONARY OcCLUSION. Myron Prznxmetal, M.D.; H. C. Bergman, Ph.D.; H. E. Kruger, M.D.; Lois Schwartz, M.D.; Benjamin Simkin, M.D.; and Sidney S. Sobin, M.D., Los Angeles. Radioactive red cells were injected intravenously into moribund patients and the distribution of the red cells in the heart was determined after death by means’ of direct Geiger counts and radioautographs of the heart. In two human hearts with myocardial infarction, the number of red cells was the same in the infarcted and normal areas of the heart. These unexpected findings prompted a series of acute experiments in dogs. A branch of the left coronary artery was ligated. Radioactive red ce& were injected intravenously and later the heart was stopped by freezing. The distribution of red cells was determined. The red cells were distributed throughout the entire heart within one minute after injection. The quantity of circulating blood in the pericardial surface of the ischemic area was equal to that of the surrounding control areas. In order to determine if collateral blood came from Thebesian vessels or anastomoses from other coronaries, fluorescein was injected intravenously in animals with ligated coronary arteries. The fluorescein was seen to enter the ischemic area from contiguous areas. It was therefore concluded that the collateral circulation to the ischemic area was derived from anastomotic channels between the coronary arteries.

HEMOLYTIC ANEMIAS, CONGENITAL AND AcQUIRED. Robert S. Evans, M.D., San Francisco. Observations of the longevity cells in patients with hemolytic

of transfused anemia have