Org 7797: A New and Unusual Antiarrhythmic Agent

Abstract

Key Words: Antifibrillatory drugs--Cardiac c y c l e a r g 7797.Pharmacological studies have shown that Org 7797 is a potent antifibrillatory agent with additional class Ic antiarrhythmic properties. Its antifibrillatory effects are manifested at the ventricular and supraventricular levels and can be explained by prolongation of wavelength at short cycle lengths leading to the prevention of deterioration of reentrant ventricular tachycardia (VT) to ventricular fibrillation (VF). This appears to result from drug-induced lengthening of refractoriness outweighing slowing of conduction which may, in turn, be a consequence of frequency-dependent prolongation of action potential duration. Org 7797 thus possesses an unusual and interesting electrophysiological profile. Higher doses of the drug are required to prevent or suppress arrhythmias of automatic origin in the dog. The dose required to suppress late ischemia-induced tachycardia, an arrhythmia dependent on sodium channel block for its termination, is four times higher than the dose required to prevent early ischemia-induced VF. Moreover, therapeutic plasma levels of the dose required for suppression of late VT are similar to concentrations required to reduce the maximum rate of depolarization of cardiac cells in vitro. By contrast, in rats plasma levels associated with antifibrillatory activity are much lower, suggesting that the mechanisms underlying the antifibrillatory and antiarrhythmic actions of Org 7797 may be different.In animals with normal hearts and in those with either established or developing infarcts, the hemodynamic effects of intravenous Org 7797 are minimal at antifibrillatory doses. The major effects of Org 7797 in normal animals are a very minor bradycardia (~4 % ) and a modest increase in peripheral vascular resistance, the latter of which was not seen in animals with myocardial infarction. Cardiac contractility and coronary blood flow ~~ ~_ _ _ _ _ _ _ _