PREVENTION BY CALCIUM-ANTAGONISTS OF PROFIBRILLATORY EFFECTS OF CLASS-I ANTIARRHYTHMIC DRUGS IN ACUTE MYOCARDIAL-ISCHEMIA - STUDY IN PIG-HEART IN-SITU

Class I antiarrhythmic drugs do not decrease, but increase, the risk o f ventricular fibrillation in the ischemic myocardium. On the contrary , vulnerability to fibrillation related to ischemia appears to be subs tantially reduced by calcium antagonists. We assessed whether the calc ium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusio n) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecaini de (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocar dium of anesthetized, open-chest pigs. Ischemia was obtained by comple tely occluding the left anterior descending coronary artery near its o rigin. Vulnerability to fibrillation was assessed by electrical fibril lation threshold (EFT), measured with diastolic impulses of 100 msec d uration delivered at a rate of 180 beats/minute. Diltiazem did not opp ose the rise in EFT induced by flecainide in the absence of ischemia ( 6.8 +/- 1.2 to 9.9 +/- 0.9 mA, p < 0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 +/- 0.9 vs 1.3 +/- 0.6 mA, p < 0.001). By reducing calcium entry into myoc ardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration fro m 215 +/- 7 to 200 +/- 4 msec, instead of 178 +/- 6 (p < 0.001), and r educed lengthening of intraventricular conduction time from 33 +/- 5 t o 43 +/- 4 msec, instead of 53 +/- 4 (p < 0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrill atory properties of flecainide due to myocardial ischemia in dosages t hat do not adversely affect myocardial contractility or atrioventricul ar conduction to a large extent.