CALCIUM-ANTAGONISTS AND PREVENTION OF VENTRICULAR-FIBRILLATION INDUCED BY TRANSIENT OR PERSISTENT ISCHEMIA

Experimental studies have shown the limitation by calcium antagonists of the propensity to fibrillation secondary to the occlusion of a larg e coronary artery. However, this capacity, studied in the acute phase of infarction, is less obvious and still under debate. Ischemia was th erefore produced in anesthetized, open-chest pigs by complete occlusio n of the left anterior descending coronary artery according to two mod es, either near its origin during brief but increasing periods (30, 60 , 120, 180 s, etc) or half-way from this origin for a much longer time (60 min). The time course of vulnerability to fibrillation was monito red by ventricular fibrillation threshold (VFT), measured by trains of diastolic stimuli of 100 ms. Verapamil was administered in a 50 mu g/ kg dose followed by 2 mu g/kg/min infusion. 1) In the case of brief pr oximal occlusions under pacing at a constant high rate (180 beats/min) , verapamil slowed the decline of VFT from 6-8 mA to nearly 0 mA. VFT was 4.4 +/- 0.4 mA after 60 s ischemia, whereas it had already fallen to 1.8 +/- 0.3 mA (p < 0.001) in the absence of the drug. Accordingly, the onset of spontaneous fibrillation which depends on the decrease i n VFT to about 0 mA was prolonged from 2-3 to 6-9 min. Bradycardia, co ncurrently produced by verapamil, is a factor which enhances these alt erations. 2) In the case of a persistent midportion occlusion of the a rtery under sinus rate, fibrillations were similarly delayed by verapa mil from 14-25 to 23-49 min after occlusion, but they were more numero us. VFT was lowered to critical values later, but also for a longer ti me. The period propitious to fibrillation was prolonged because the re turn of VF-T to higher values reflecting hypoexcitability subsequent t o the first cell injury was substantially delayed. Consequently, calci um antagonists should often prevent ventricular fibrillation when tran sient ischemia disappears before VFT falls to the vicinity of 0 mA. In contrast, a real benefit could not be expected from these drugs when ischemia is persistent since they then only delay fibrillations, the n umber of which is increased.