[Disopyramide phosphate: electrophysiological and inotropic effects in isolated cat papillary muscles and comparison...

The effects of 4-diisopropylamino-2-phenyl-2-(2-pyridyl)-butyramide monophosphate (disopyramide phosphate; D; 10(-6)--10(-4) M) on transmembrane resting potential, action potential, effective refractory period and twitch tension were simultaneously studied in electrically driven (frequency 1 Hz) papillary muscles isolated from the right ventricles of cats. The experiments were performed at 35degrees C with intracellular glass microelectrodes. Quinidine sulfate (10(-6)--10(-4) M) was used for comparison. D increased the duration of the action potential during phase 3 (90% repolarization) in a concentration-dependent manner. The effective refractory period was prolonged by nearly the same extent whereas the maximal rate of rise of the action potential was reduced. The overshoot was slightly decreased only at 10(-4) M. Resting potential and plateau phase of the action potential were not affected by D. The effects of D on the electrical events were accompanied by concomitant decreases in twitch tension. The effects of quinidine were essentially similar to those obtained with D. It is concluded that the effects of D on dV/dtmax and effective refractory period observed in cat papillary muscle may account for the clinically observed efficacy of D to overcome ventricular arrhythmias. The results suggest also that the mechanism of the ventricular effects of D is similar to that of quinidine.