Electrophysiological actions of disopyramide phosphate on canine ventricular muscle and purkinje fibers.

Abstract

Disopyramide phosphate is a new antiarrhythmic drug that has been shown to possess significant antiarrhythmic effects in animals and man. In the present investigation, the effects of 2, 5, and 10 mug/ml of disopyramide phosphate were studied on the electrophysiological properties of canine Purkinje fibers and ventricular muscle superfused in vitro. Transmembrane action potentials were recorded from Purkinje fibers in the region of maximum action potential duration (gate), from Purkinje fibers proximal and distal to the gate, and from ventricular muscle. Disopyramide phosphate produced a concentration-dependent decrease in the slope of phase 4 diastolic depolarization of spontaneously beating Purkinje fibers. In all electrically stimulated fibers, the drug decreased the amplitude and the maximum upstroke velocity of the action potential. This depression of phase 0 characteristics was accompanied by a decrease in conduction velocity. In Purkinje fibers located at the gate, a concentration-dependent parallel shift to the right and a depression of the maximum of the membrane responsiveness curve occurred. Effects on action potential duration were variable. Repolarization was altered so that action potentials with dissimilar durations recorded from sites proximal to, at, and distal to the gate became equal. The total action potential duration and the effective refractory period of gate Purkinje fibers were prolonged, but the change in action potential duration was always greater than the change in effective refractory period so that the ratio of the change in duration to the change in refractory period was always greater than one.