The electrophysiologic effects of ersentilide on canine hearts

Ersentilide is a benzamide derivative that has been found effective in several intact animal models of arrhythmia. Cellular studies have indicated it blocks the delayed rectifier, IK, and is a beta 1-adrenoceptor antagonist. We used standard electrophysiologic techniques to study ersentilide's actions on canine Purkinje fiber and atrial and ventricular myocardium. Ersentilide had no effect on maximum diastolic potential, action potential amplitude or Vmax of any of those tissues. Neither did it affect normal Purkinje fiber automaticity. Ersentilide prolonged action potential duration and effective refractory period, and prolonged the duration of Ca(2+)-dependent 'slow response' action potentials. It also suppressed abnormal automaticity in Ba2+ superfused fibers and attenuated isoproterenol-induced automaticity. Although ersentilide increased the magnitude of digitalis-induced delayed afterdepolarizations it neither increased nor suppressed the incidence of digitalis-induced arrhythmias in intact dogs. Because it selectively prolongs action potential duration and refractoriness and induces beta 1-adrenoceptor blockade, ersentilide warrants further consideration as an antiarrhythmic agent.