Coupling Interval-Related Effects of Class I Antiarrhythmic Drugs, Mexiletine, Cibenzoline and Disopyramide, on Ventricular Activation in Canine Myocardial Infarction.

Abstract

Time-dependent inhibition of sodium channels by class I antiarrhythmic drugs has been observed in isolated cardiac muscles or cells. We examined coupling interval-related effects of class I antiarrhythmic drugs, mexiletine, cibenzoline and diso pyramide, on ventricular activation in canine infarcted myocardium. A ventricular stimulation with various coupling intervals was applied to the right ventricle, and activation delays (time intervals between the initiation of a deflection and the final rapid deflection of a bipolar electrocardiogram) of infarcted and normal zones were measured. The premature stimulation produced a delayed activation and in some animals, caused reentrant beats. Mexiletine (3 and 10 mg/kg), cibenzoline (1 and 4 mg/kg) and disopyramide (1 and 4 mg/kg) further enhanced or blocked the delayed activation. The effects of these drugs were more marked at shorter coupling intervals, although cibenzoline and disopyramide showed significant effects also at long coupling intervals. The effect of these drugs on the activation in the normal zone was less than that in the infarcted zone. In conclusion, mexiletine, cibenzoline and disopyramide showed a coupling interval-related depression of delayed activation in infarcted myocardium, which may be a reflection of their time-dependent inhibition of sodium channels.

Electrophysiologic effects of volatile anesthetics, sevoflurane and halothane, in a canine myocardial infarction model

“…A similar effect was observed with class I antiarrhythmic drugs [16], which may be caused by a time-dependent inhibition of sodium channels [27]. However, it is not clear whether or not the mechanism of the coupling interval-related effects of the volatile anesthetics is similar to those of class I antiarrhythmic drugs.…”

“…The present study showed that sevoflurane depressed the delayed activation in infarcted zones of canine ventricles. The effect of sevoflurane was selective to the A selective depression of the delayed activation was observed with class I antiarrhythmic drugs [16]. A previous study showed that halothane decreased the Vm in the isolated Purkinje fibers of infarcted hearts [8].…”

“…A markedly delayed activation may lead to reentrant arrhythmias, and the blockade of the activation with antiarrhythmic drugs prevents arrhythmias [16,[21][22][23]. In the two animals in which ventricular ~r"h'"hmias were induced by the premature stimulation, which were suppressed during the inhalation of sevoflurane or halothane.…”