DELAY BY A CALCIUM-ANTAGONIST, AMLODIPINE, OF THE ONSET OF PRIMARY VENTRICULAR-FIBRILLATION IN MYOCARDIAL-ISCHEMIA

Calcium antagonists have been reported to counteract the increase by i schemia of vulnerability to ventricular fibrillation. This ability mig ht be especially of interest in the prevention of sudden death subsequ ent to a major, but transitory, inadequacy between myocardial oxygen r equirements and available coronary blood flow produced by exercise, em otion, etc., because death is then not related to irreversible damage of myocardial fibers. This study has been undertaken to examine the pr otective effect of a calcium antagonist on an animal model of this typ e of ischemia. This model used complete, but transient occlusion of th e left anterior descending coronary artery near its origin during paci ng at a constant high rate (180 beats/min) in anesthetized, open-chest pigs, most often resulting in fibrillation within 1-2 minutes after a progressive fall of the electrical fibrillation threshold. Amlodipine was the preferred calcium antagonist for this study because it is onl y moderately negatively inotropic. The results of the preventive admin istration of amlodipine was assessed by the time to onset of fibrillat ion. Amlodipine 0.30 mg/kg prolonged this time by 50-100% (p < 0.05) w ithout appreciable impairment of blood pressure or myocardial contract ility. Concurrently, amlodipine delayed the shortening of the monophas ic action potential duration, the lengthening of conduction time, and the alterations of ST segments and T waves linked to ischemic depolari zation. Consequently, when given experimentally before the occurrence of major, but transitory ischemia, amlodipine protected against fibril lation. Similarly, in clinical settings it ought to delay sudden death that may occur as a result of a major but transitory inadequacy betwe en myocardial oxygen requirements and available coronary blood flow.