Cardiac effects of cibenzoline

Abstract

The effects of cibenzoline were examined in the dog with multifocal ventricular arrhythmias 24 h after ligation of the left anterior descending coronary artery, and on isolated, superfused canine cardiac tissues which were studied using standard microelectrode techniques. In the intact dog, 5 mg/kg cibenzoline consistently exerted antiarrhythmic effects. In all experiments, the percentage of normal sinus beats was greatly increased as the ventricular ectopic cycle length was significantly prolonged. Cibenzoline also slightly decreased the mean sinus cycle length. In isolated, driven Purkinje fibers, cibenzoline (1-5 mg/L) exerted lidocaine-like effects, significantly shortening the plateau of the action potential and decreasing the maximum rate of depolarization. Cibenzoline (2.5 mg/L) did not decrease the rate of normal automaticity in Purkinje fibers (with maximum diastolic potentials [MDPs] greater than - 85 mV), but did slow the rate of fibers pretreated with isoproterenol (0.5-10 microM) for greater than 30 min. It did not slow these fibers via beta-adrenergic blockade, because superfusion of cibenzoline-pretreated fibers with isoproterenol (0.5-10 microM) produced positive chronotropic responses which were as large as those that occurred in these fibers prior to cibenzoline exposure. Cibenzoline, 1-5 mg/L, also significantly slowed "abnormal automaticity" in Purkinje fibers with MDPs of -60 to -40 mV. In experiments on automaticity in fibers with normal MDPs, cibenzoline, 2.5-5.0 mg/L, was found to induce early afterdepolarizations and triggered activity within 16-30 min of the start of exposure. These early afterdepolarizations could be terminated by stimulating the fibers at cycle lengths of 2,000 ms or less. The antiarrhythmic actions of cibenzoline may result from negative chronotropic effects on abnormal automaticity or on catecholamine-induced (triggered) automaticity, or from effects on conduction dependent on its local anesthetic actions.