POSSIBLE PREVENTION BY AMLODIPINE OF VENTRICULAR-FIBRILLATION RELATEDTO BRIEF ISCHEMIA EPISODES

Calcium antagonists may reduce propensity to ventricular fibrillation, by altering the balance between coronary blood flow and metabolic dem and, and thus may substantially prolong time to occurrence of fibrilla tion. This delay in the onset of fibrillation should be sufficient to prevent sudden death in the case of transitory episodes of myocardial ischemia. Therefore, this study was based on the determination of time to onset of fibrillation in an animal model of transitory ischemia. T his model was achieved by the complete, but transitory occlusion of th e left anterior descending coronary artery near its origin under ventr icular pacing at a constant high rate (180 beats/min), in anesthetized , open-chest pigs. Amlodipine was preferred to another calcium antagon ist for this study because it is among the least negatively inotropic of these drugs. It was intravenously infused at 0.02 mg . kg(-1). min( -1). Time to fibrillation was prolonged from 87 +/- 10 to 146 +/- 16 s (p < 0.05) with the 0.30 mg/kg dose and to 201 +/- 22 s (p < 0.05) wi th the 0.60 mg/kg dose, without serious impairment of blood pressure o r left ventricular dP/dt(max) in the absence of ischemia. Concurrently , amlodipine significantly limited the shortening of monophasic action potential duration (200 +/- 4 vs. 172 +/- 6 ms), the lengthening of c onduction time (43 +/- 2 vs. 53 +/- 2 ms), and the alterations of ST s egments and T waves induced by 60 s ischemic depolarization. Consequen tly, amlodipine might reduce the incidence of sudden death by lengthen ing time to onset of fibrillation beyond the duration of the ischemia, when transitory.