Effects of aprindine and disopyramide on reperfusion-induced arrhythmias and cardiac function in isolated rat hearts.

The effects of aprindine and disopyramide on reperfusion-induced arrhythmias and cardiac function were investigated in the isolated perfused rat heart. Occlusion of the left anterior descending coronary artery for 15 min and subsequent reperfusion provoked ventricular tachycardia in 9 out of 10 hearts and ventricular fibrillation in 7 out of 10. Aprindine or disopyramide was infused 15 min prior to the coronary occlusion in concentrations of 0.1 and 5.4 micrograms/ml, which were comparable to therapeutic free plasma concentrations in patients. Aprindine significantly decreased the incidence of ventricular tachycardia and fibrillation, compared with control (2/10, p less than 0.01 and 1/10, p less than 0.05, respectively). Disopyramide depressed only the occurrence of ventricular tachycardia (3/10, p less than 0.05). Neither of the drugs induced changes in heart rate, left ventricular systolic pressure, coronary flow or PR intervals, but they significantly improved the recovery of the left ventricular systolic pressure within 15 min after reperfusion, at which time most of the hearts had restored sinus rhythm. It is concluded that, at clinically effective concentrations, aprindine and disopyramide inhibit reperfusion-induced arrhythmias without deteriorating cardiac function in the isolated rat heart.