Electrophysiologic effects of a new anitarrhythmic agent, recainam, on isolated canine and rabbit myocardial fibers

Abstract

Recainam (Wy 42,362) is a new antiarrhythmic agent undergoing clinical evaluation, but its electrophysiologic effects in cardiac muscle are poorly defined. With microelectrode techniques, its profile in isolated preparations of dog and rabbit hearts was determined using drug concentrations of 10 to 300 μM. Recainam induced a concentration and frequency-dependent decrease in the maximal rate of rise of ihe phase 0 of the action potential (Vmax), action potential amplitude and overshoot potential, with little or no change in the effective refractory period except in Purkinje fibers, in which it was markedly reduced. At a 300 μMconcentration, Vmaxwas reduced 51% (p < 0.001) in ventricular muscle and 44% (p < 0.001) in atrial muscle, with no change in action potential duration or effective refractory period. At the same drug concentration in Purkinje fibers, Vmaxwas decreased by 41% (p < 0.01), action potential duration at 90% repolarization by 36% (p < 0.01) and effective refractory period by 34% (p < 0.01). Recainam had no significant effect on the sinoatrial node, but it depressed phase 4 depolarization in isoproterenol-induced automaticity in Purkinje fibers. The drug had no effect on slow channel potentials induced by high concentrations of potassium and isoproterenol.The data indicate that the electrophysiologic profile of recainam in isolated cardiac muscle is consistent with the overall effects of class IC agents without having an effect on the slow calcium channel. Its major action is to depress Vmax, with little effect on refractoriness. As in the case of other class IC compounds, the differential effects of recainam on the action potential duration in ventricular muscle and Purkinje fibers may predispose to the drug's proarrhythmic actions by accentuating heterogeneity in refractoriness in the heart.