Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats.min-1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg.kg-1 plus 0.02 mg.kg-1.min-1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.

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The effects of three Ic antiarrhythmic drugs, flecainide, propafenone and cibenzoline, were investigated in anaesthetized, open-chest pigs, in a left ventricular area, during pacing at a constant high rate (180 beats min-1), in the absence and the presence of ischaemia. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery 1-1.5 cm from its origin. In addition to surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of the effective refractory period was added in the absence of ischaemia. In this event, flecainide and propafenone, each in a dose of 2.5 mg kg-1 i.v. and cibenzoline, 2.0 mg kg-1, i.v., considerably lengthened (by 50-90%) conduction time, but did not affect or hardly affected the duration of the monophasic action potential or the effective refractory period. Thus, it seems that these Ic antiarrhythmic drugs enhance the prolongation of conduction time by 60% and do not prevent the 30% shortening of monophasic action potential caused by ischaemia: contrary to expectation, they produced a large reduction (from about 120 to 25 s) in the onset time of fibrillation due to ischaemia. Thus, they manifested profibrillatory properties (more pronounced than those of other class I antiarrhythmic drugs), which might be explained by their potent action on depolarization with almost total absence of action on repolarization.

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