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European Heart Journal 1983 4(7):512-520;
Copyright © 1983 by the European Society of Cardiology.
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© 1983, by the European Society of Cardiology

Intracardiac electrophysiological study of S–2395 in intact and chemically sympathectomized dogs

C. GUIMOND, C. VASSEUR, D. GODIN, A. R. LEBLANC and R. NADEAU

Centre de Recherche, Hôpital du Sacré-Coeur, and Department of Physiology, Faculty of Medicine Université de Montréal, Montréal, Québec, Canada

Received 18 March 1982; revised 20 October 1982; .

Requests for reprints: Claude Guimond, Centre de Recherche, Hôpital du Sacré-Coeur. 5400 Boulevarde Gouin Ouest. Montréal, Quebec, Canada H4J IC5.

Abstract

S-2395 is a new, long-acting, non-selective ß-receptor blocking agent without apparent intrinsic cardiodepressive action and no receptor selectivity. Its electrophysiological actions were studied in infact and chemically sympathectomized dogs.

In normal dogs, S-2395 very slightly increased atrial monophasic action potential (MAP a) duration, atrioventricular functional (FRP) and ventricular effective (ERP) refractory periods. The onset of the atrial supernormal conduction phenomenon (SNCP) was delayed and the ventricular SNCP was abolished. These results are consistent with the action of low concentrations of ß-blocking agents. In contrast S-2395 reduced the ventricular MAPv and increased the ERP/MAPv ratio of sympathectomized animals. Such modifications are usually seen with concentrations higher than necessary for simple ß-receptor blockade.

In conclusion S-2395, like several others ß-blockers, had minor effects on the classical electrophysiological parameters of normal dogs. However, it suppressed ventricular SNCP and had a more pronounced action in sympathectomized dogs who are known to have higher levels of circulating catecholamines and who present post-synaptic supersensitivity. The SNCP has been linked with re-entrant arrhythmias. Considering that ß-blockers prevent arrhythmias specially in hyperadrenergic states, the suppression of the ventricular SNCP by S-2395 could thus be the mechanism by which this drug and possibly other ß-blockers might exert their antiarrhythmic action.

Key Words: Cardiac electrophysiology • S-2395 • 6-hydroxydopamine • monophasic action potentials • ß-blocking agents


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