Effects on rabbit cardiac potentials of aprindine and indecainide, a new antiarrhythmic agent, in normoxia and hypoxia

Abstract

Intracellular potentials were recorded from rabbit atria, cardiac Purkinje cells and papillary muscles before and after exposure to various concentrations of indecainide. The effects of aprindine also were studied in the atrial preparations. Both drugs depressed the maximum rate of depolarization (MRD) in a dose-related manner, indecainide being approximately ten times more potent than aprindine. Aprindine caused a dose-related bradycardia, but indecainide had no significant effect on sinus node frequency. Indecainide had a dose-related negatively inotropic effect in normal, half-normal and twice-normal extracellular calcium concentrations. Indecainide shortened action potential duration (APD) in atrium and Purkinje cells but prolonged APD to 50% repolarization in ventricular muscle. The actions of indecainide were extremely persistent. No significant recovery of MRD was observed after pauses in stimulation of up to 16 s. Indecainide had no effect on effective refractory period (ERP) measured by interpolated premature stimuli. Indecainide is therefore categorized as a Class 1c antiarrhythmic agent. The effects of both aprindine and indecainide on MRD were increased in hypoxic atria. Conduction velocity in hypoxic atria exposed to indecainide was greater than in controls, however, suggesting the possibility of improved cell-to-cell coupling.