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(Circulation. 1974;49:272.)
© 1974 American Heart Association, Inc.

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Antiarrhythmic Properties of Chlordiazepoxide

RICHARD A. GILLS PH.D.¹; HAROLD THIBODEAUX ¹; LOUIS BARR M.D.¹

¹ From the Department of Pharmacology, Georgetown University Schools of Medicine and Dentistry, Washington, D.C.

The reported effectiveness of chlordiazepoxide in depressing the central nervous system led us to test this agent against cardiac arrhythmias induced by digitalis and coronary occlusion. The digitalis studies were performed in Dial-urethane anesthetized cats by monitoring: (1) ECG, (2) femoral arterial blood pressure, (3) right ventricular contractile force, and (4) spontaneous activity in cardiac sympathetic nerves. Chlordiazepoxide (3.6-39.5 mg/kg i.v.) converted established ventricular arrhythmias induced by deslanoside to regular sinus rhythms in nine of the 12 animals studied. Conversion was associated with depression of deslanoside-induced sympathetic nerve firing. Chlordiazepoxide was ineffective against similar arrhythmias produced in eight spinal-sectioned cats. The coronary occlusion studies were performed in unanesthetized dogs 1 day after two-stage ligation of the anterior descending branch of the left coronary artery. The ECG was recorded and all dogs exhibited ventricular ectopic beats. Chlordiazepoxide (10 mg/kg i.v.) produced a significant reduction in the number of abnormal beats, a significant increase in sinus beats, and a significant degree of cardiac slowing. The effect of chlordiazepoxide on the antiarrhythmic and central nervous system effects of lidocaine was also tested in this preparation. Pretreatment with chlordiazepoxide enhanced the antiarrhythmic effect and prevented the neurotoxic effect of lidocaine. These results support our hypothesis that drugs which depress the central nervous system may be effective for the treatment of ventricular arrhythmias. These results also demonstrate the potential benefit of combining chlordiazepoxide with lidocaine in antiarrhythmic drug therapy.

Key Words: Deslanoside • Sympathetic nerve activity • Coronary occlusion • Lidocaine • Contractile force • Blood pressure

Submitted on June 20, 1973
Accepted on September 24, 1973