Clofilium1--a new antifibrillatory agent that selectively increases cellular refractoriness

Abstract Clofilium is the most promising member in a new series of antifibrillatory agents to selectively prolong cardiac action potential duration (APD) and effective refractory period (ERP). In normal superfused canine Purkinje fibers, clofilium prolonged APD and ERP by a maximum of 35% (ED 50 =1.3 × 10 −8 M). The effect of clofilium reached equilibrium in 61±3 min but APD did not return toward control during several hr of superfusion with drug-free medium. No change in rate of rise, amplitude, resting potential or rate of diastolic depolarization was noted in the presence of clofilium (3 × 10 −7 M). Clofilium increased the canine ventricular fibrillation threshold (VFT) measured using gated trains of electrical stimuli. This effect occurred in a dose-related fashion following a 30 min infusion of a total of 0.5 or 1.0 μmole/kg of clofilium. The increase was evident within 30 min after ending the infusion and persisted for at least 4 hr. Following the infusion of clofilium (1.0 μmole/kg) 22% of the episodes of ventricular fibrillation (VF) spontaneously reverted to normal sinus rhythm without the use of direct current countershock; this phenomenon did not occur in dextrose-infused dogs.