Antiarrhythmic and electrophysiologic effects of bepridil in chronically infarcted conscious dogs

The antiarrhythmic and antifibrillatory actions of bepridil, an antianginal agent with cardiac fast and slow channel-blocking activities, were evaluated in conscious dogs 3 to 7 days after anterior myocardial infarction. The i.v. administration of 5.0 mg/kg of bepridil prevented the initiation of ventricular tachycardia in four of 12 postinfarction dogs tested and slightly but significantly prolonged the effective refractory period determined at the right ventricular outflow tract. The i.v. administration of 10.0 mg/kg of bepridil prevented ventricular tachycardia induction in seven of 13 dogs tested and significantly reduced the rate of the induced tachycardia in the remaining six dogs. Significant increases in ventricular activation times measured in both normal and infarcted areas of myocardium, as well as a modest prolongation in ventricular refractoriness, accompanied administration of 10.0 mg/kg of bepridil. Acute pretreatment with 5.0 and 10.0 mg/kg of bepridil produced a dose-dependent and significant (10.0 mg/kg) delay in the development of ventricular fibrillation in response to ischemia at a site remote from previous myocardial infarction, as well as suggestive increases in survival 24 hr after the development of ischemia. These results suggest that bepridil may possess antiarrhythmic properties useful in the management of recurrent ventricular tachycardia in the setting of myocardial infarction and in the suppression of early ischemia-mediated ventricular fibrillation in the presence of previous myocardial injury.