ZATEBRADINE SLOWS ECTOPIC VENTRICULAR RHYTHMS IN CANINE HEART 24 HOURS AFTER CORONARY-ARTERY LIGATION

Arrhythmias occur 24 h after occlusion of the left anterior descending (LAD) coronary artery in the canine heart and have been attributed to the abnormal spontaneous activity in subendocardial Purkinje fibers, which are markedly depolarized. The major current underlying normal au tomaticity in these fibers is if. Although the if activation range is generally considered to be more negative than the diastolic membrane p otential in these depolarized fibers in infarcts, this activation rang e has been shown to shift in a positive direction in response to hormo nal influences. Thus if could still mediate automaticity in these fibe rs in infarcts. Furthermore, recent reports indicate that a depolarizi ng diastolic current, probably if, also can be measured in ventricular muscle during abnormal experimental conditions, which may occur durin g ischemia. To test whether there is a role of if currents in sustaini ng ventricular ectopy, we administered the selective if channel blocke r, zatebradine, 24 h after LAD ligation in canine hearts. We report th at intravenous injections of zatebradine (0.25 or 1.0 mg/kg) significa ntly slow ventricular rhythms (with average reductions of 19 or 26%, r espectively). Moreover, because zatebradine also slows sinus nodal rat e, it can lead to an increased incidence of ectopic beats. However, du ring right atrial pacing, when sinus slowing has no effect on ventricu lar rhythms, capture of ventricular rhythms occurs at lower rates in t he presence of zatebradine. The reduction of capture threshold is comp arable to the reduction in the rate of the ectopic rhythm. Thus zatebr adine eliminated the arrhythmia when the right atrium was paced at the original sinus rate.