Class Ic antiarrhythmic drugs and myocardial ischaemia: study in the pig heart in situ

Abstract

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.

Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine

“…The contractile fibers possessing the most negative potential exhibit the most delayed activation. The behavior of bupivacaine resembles that of the IC antiarrhythmic drugs, such as flecainide (21)(22)(23)(24)(25), which depress intraventricular conduction to a great extent on account of a strong influence on sodium channel in moderate doses which have little effect on repolarization. As these drugs have been shown by multicenter, randomized, placebo-controlled trials (26,27) to be likely to increase the incidence of sudden death, instead of decreasing it as expected, similar accidents were possible with bupivacaine.…”

The effects of ropivacaine at clinically relevant doses on myocardial ischemia in pigs

“…In addition, ropivacaine also induced a significant reduction in VFT under ischemia, an effect which is very similar to that shown with other local anesthetic drugs and class I antiarrythymic drugs [11,12]. Myocardial ischemia generates ventricular fibrillation, and various ischemia-related alterations are thought to be involved, including changes in the synthesis and/or degradation of sarcolemma membrane proteins [13], changes in gap junctions [14], and changes in the membrane polarity of cardiomyocytes [15].…”

Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs

“…The occlusion of the left anterior descending coronary artery allowed the circulation to he inteiyupted comple-tely in an area of the left ventricle corresponding roughly to the half of its anterior wall, until the triggering of fibrillation which ordinarily occurs within 100-120 s under ventricular pacing at 180 bpm. This technique, which we had set up for the study of profibrillatory properties of I, drugs (Timour et al, 1991). was used in the present work to study the alterations in conduction preceding fibrillation.…”