Supraventricular antidysrhythmic and electrophysiological effects of bepridil, a new antianginal agent

We investigated the potential antidysrhythmic effects of bepridil, a new antianginal agent, on dysrhythmias of supraventricular origin. Intravenous bepridil (5 mg/kg) suppressed dysrhythmias evoked by local application of aconitine to the left atria of anesthetized cats. After the aconitine-induced dysrhythmias had subsided, cardiac function was better maintained in animals given bepridil than in the controls. The effects of bepridil on the maximum following frequency (MFF) and transmembrane action potentials of isolated guinea pig atria and on cells displaying phase 4 depolarization were also examined. Both bepridil (5--120 microM) and verapamil (0.02--1 microM) induced a dose-dependent reduction in contractility of driven left atria, whereas only bepridil reduced MFF. The effects of bepridil (10--40 microM) on the cellular action potentials of left atria were a dose-dependent decrease in the maximum rate of depolarization of phase 0 associated with a reduction in action potential height and a marked prolongation of the action potential duration. In similar concentrations, bepridil reduced the spontaneous rate of the right atrium and reduced the slope of phase 4 depolarization. We conclude that the action of bepridil in suppressing supraventricular dysrhythmias may be partly explained by depression of automaticity together with a reduction in the intensity of the inward sodium current.