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 large coronary artery. However, this capacity, studied in the acute phase of infarction, is less obvious and still under debate. Ischemia was therefore produced in anesthetized, open-chest pigs by complete occlusion of the left anterior descending coronary artery according to two modes, 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 monitored by ventricular fibrillation threshold (VFT), measured by trains of diastolic stimuli of 100 ms. Verapamil was administered in a 50 micrograms/kg dose followed by 2 micrograms/kg/min infusion. 1) In the case of brief proximal 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 in VFT to about 0 mA was prolonged from 2-3 to 6-9 min. Bradycardia, concurrently produced by verapamil, is a factor which enhances these alterations. 2) In the case of a persistent midportion occlusion of the artery under sinus rate, fibrillations were similarly delayed by verapamil from 14-25 to 23-49 min after occlusion, but they were more numerous. VFT was lowered to critical values later, but also for a longer time. The period propitious to fibrillation was prolonged because the return of VFT to higher values reflecting hypoexcitability subsequent to the first cell injury was substantially delayed. Consequently, calcium antagonists should often prevent ventricular fibrillation when transient 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 number of which is increased.