DISAPPEARANCE WITH ISCHEMIC DEPOLARIZATION OF THE ANTIFIBRILLATORY ACTIVITY IN A SODIUM-CHANNEL BLOCKER AND APPEARANCE IN A CALCIUM-CHANNELBLOCKER

Results obtained in the prevention of ventricular fibrillation seconda ry to myocardial ischaemia are unexpected. Profibrillatory properties might be manifested by Class I antiarrhythmic drugs, normally antifibr illatory. Clear antifibrillatory properties might be manifested by cal cium channel blockers, the antifibrillatory effects of which are norma lly questionable. Therefore, the action of a Class I antiarrhythmic dr ug, flecainide, and of a calcium channel blocker, verapamil, on the vu lnerability to ischaemic ventricular fibrillation was assessed in anae sthetized, open-chest pigs by ventricular fibrillation threshold. Vent ricular fibrillation threshold was determined with trains of diastolic stimuli of 100 msec duration, delivered at a rate of 180 beats/min (n ear that of the ventricular tachycardia), by a subepicardial electrode inserted into the area that could be subjected to ischaemia. Before d etermining this threshold, ventricles were paced at the same rate, par ticularly during the ischaemic periods. Ischaemia was produced by comp lete occlusion of the left anterior descending coronary artery, either at its origin or half-way from it, over increasing periods. The monop hasic action potential and conduction time were recorded in the ischae mic area. Before ischaemia, flecainide was adapted to raise the ventri cular fibrillation threshold, in spite of a lengthening of the conduct ion time. Verapamil was devoid of any influence on these parameters. T he antifibrillatory effect of flecainide disappeared with ischaemia, w hich reduced the ventricular fibrillation threshold down to near 0 mA, with triggering of the spontaneous fibrillation at this level: this r eduction was no longer counteracted and even hastened by flecainide, b ecomes finally profibrillatory. Verapamil, on the contrary, delayed th e fall in ventricular fibrillation threshold, maintained far from 0 mA , with prevention of fibrillation, unless the occlusion was maintained over a much longer period. Verapamil similarly delayed the shortening of the monophasic action potential duration and the lengthening of th e conduction time, preceding fibrillation and leading to it. Consequen tly, ischaemic depolarization is apparently responsible for the loss o f antifibrillatory activity in a sodium blocker, such as flecainide, a nd the development of antifibrillatory activity in a calcium blocker, since the sodium channel is activated only at high potentials, whereas the calcium channel is activated at lower potentials.