Key result
Ersentilide prolongs refractoriness, suppresses abnormal automaticity, and induces beta-1 blockade in canine myocardium.
Why the study?
Ersentilide's electrophysiologic effects on canine cardiac tissues and its potential as an antiarrhythmic agent were not fully characterized.
Does ersentilide alter electrophysiologic properties and automaticity in canine cardiac tissues?
Does ersentilide alter electrophysiologic properties and automaticity in canine cardiac tissues?
Ersentilide demonstrates a promising antiarrhythmic profile by selectively prolonging action potential duration and refractoriness and inducing beta 1-adrenoceptor blockade in canine models.
No effect on conduction parameters in canine tissues; leaves open antiarrhythmic translation to clinical use.
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.
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Lee et al. (1995) studied Arrhythmia (animal model). Ersentilide was evaluated on Electrophysiologic effects (action potential duration, effective refractory period, automaticity). Ersentilide prolonged action potential duration and effective refractory period, suppressed abnormal automaticity, and induced beta 1-adrenoceptor blockade in canine hearts.
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