Arrhythmogenic effects of toxic concentrations of the antiarrhythmic drug lorcainide on the isolated canine ventricle.
The effect of the new antiarrhythmic drug lorcainide was studied on the specialized conducting system of isolated canine ventricle. Transmembrane action potentials were recorded simultaneously from three subendocardial sites within the ventricular basis, free wall and apex. At concentrations of 3 x 10(-6) and 2.4 x 10(-5) M, lorcainide caused a dose-dependent decrease in maximum rates of rise and in amplitude of the action potential; 0.6 x 10(-6) M had no significant effect, resting potential and action potential duration remained unchanged with 0.6 x 10(-6) M and 3 x 10(-6) M. The most prominent effect of 2.4 x 10(-6) M lorcainide was the appearance of an increasing notch resulting in clear separation of the action potential in an initial short spike depolarization (50-120 msec) with or without a subsequent plateau depolarization 280-370 msec). Both components demonstrated an independent and inhomogeneous conduction through functionally different pathways. Changes in stimulation rate or premature stimuli resulted in nonstimulated reexcitations resembling bigemini, ventricular tachycardia or regional ventricular fibrillation. The results indicate that dissociation of the action potential in two components is due to toxic alterations of ionic channels of the fiber membrane and that nonstimulated reexcitations are due to reentry via functionally fast and slow pathways.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D044482:Benzeneacetamides; D004285:Dogs; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D010880:Piperidines; C015970:lorcainide