Electrophysiologic effects of E-4031, a class III antiarrhythmic agent, on re-entrant ventricular arrhythmias in a canine 7-day-old myocardial infarction model.

Effects of E-4031, a class III antiarrhythmic agent, on re-entrant ventricular arrhythmias were studied in eight dogs with a 7-day-old myocardial infarction. Epicardial mapping and local refractory periods were obtained using 47-channel bipolar electrodes attached to the epicardium. The induction of sustained ventricular tachycardia by programmed electrical stimulation was not suppressed by i.v. infusion of E-4031 at 1 microgram/kg/min, but was suppressed markedly by infusion at 10 micrograms/kg/min in six of seven dogs. During the infusion of E-4031 at 10 micrograms/kg/min, epicardial conduction velocity in the normal ventricle did not change (0.7 +/- 0.12 to 0.71 +/- 0.13 m/sec, n = 6), whereas slowed conduction in the infarct zone improved (0.58 +/- 0.10 to 0.77 +/- 0.13 m/sec, n = 6). E-4031 at 10 micrograms/kg/min prolonged effective refractory periods (ERP) in the normal zone (139 +/- 8 to 164 +/- 18 msec, P less than .01, n = 8), nontransmural infarct zone (145 +/- 7 to 177 +/- 15 msec, P less than .01, n = 8) and transmural infarct zone (156 +/- 14 to 191 +/- 22 msec, P less than .01, n = 8). The degrees of ERP prolongation were almost equal in all zones. On epicardial mapping, the areas of longer ERP and delayed conduction were observed to become inexcitable after the administration of E-4031. These results demonstrated that E-4031 effectively prevented the induction of re-entrant ventricular tachycardia in canine myocardial infarction model, and suggested that E-4031 rendered re-entrant circuits inexcitable by marked ERP prolongation in both normal and infarct zones.