Electrophysiological effects of encainide on isolated cardiac muscle and purkinje fibers and on the Langendorff-perfused guinea-pig heart

Abstract

The effect of encainide (0.1, 0.3 and 1.0 mg/l) on transmembrane electrical activity was studied in left auricle and papillary muscles of the guinea pig and in Purkinje fibers of cow and sheep hearts. Conduction times and refractoriness of the AV node and the His-Purkinje system were measured in the Langendorff-perfused guinea-pig heart by His-bundle recording. Encainide had no effect on the maximum diastolic potential. Action potential duration (100% repolarization) remained constant or slightly prolonged in guinea-pig auricle and ventricle preparations but was shortened in cow and sheep Purkinje fibers. Action potential amplitude and V max decreased in a dose-dependent manner, the effect being more pronounced at higher frequencies. The frequency effect was not related to a change in the recovery of V max following the repolarization. The drug reduced V max at all membrane potential values, the relative effect being slightly more pronounced at low membrane potentials. In three different tests for pacemaker activity encainide had no effect on the rate of diastolic depolarization at high levels of membrane potential, but clearly reduced the spontaneous oscillations at the plateau level and the transient depolarizations characteristic for triggered pacemaker activity induced by ouabain. Ca-mediated action potentials were not affected even at concentrations of encainide up to 8 mg/l. In the Langendorff-perfused guinea-pig heart, conduction through the His-Purkinje system was slowed more than conduction through the AV node. All effects were quickly reversible by drug-free perfusion. In comparison with lidocaine, the effect of encainide on electrical parameters showed the following differences: the decrease in V max in the presence of encainide was more frequency-dependent, and less potential-dependent, the effect of encainide on pacemaker activity was more selective.