Comparative electrophysiological effects of the second generation antihistamines, astemizole and ebastine, in a canine myocardial infarction model

Abstract

In this study, the effects of the histamine H 1 receptor antagonists, astemizole, and ebastine on RT intervals, ventricular action, effective refractory periods (ERPs), and programmed electrical stimulation (PES)-induced ventricular arrhythmias were investigated in canine hearts with myocardial infarction produced by two-stage ligation of the left anterior descending coronary artery. Seven days postligation, bipolar electrodes were sutured on the ventricular surface in infarcted and intact zones to either electrically stimulate or record ventricular activation. The RT interval was measured in the intact zone. The ERPs in infarcted and intact zones were determined during atrial pacing. Ventricular activation delay was measured during premature excitation produced by stimulation at a coupling interval between 120 and 300 ms on the ventricular surface in the intact zone. The RT interval was significantly (P < 0.05) prolonged by astemizole. In addition, the prolongation of the RT interval was greater at longer coupling intervals. In contrast, ebastine did not affect the RT interval. Astemizole at doses of 0.3-3.0 mg/kg significantly (P < 0.05) prolonged the ERP; ebastine at a dose of 3.0 mg/kg also prolonged the ERP in both intact and infarcted zones. Astemizole at doses of 0.3-3.0 mg/kg prolonged ventricular activation delay; ebastine at a dose of 3.0 mg/kg also prolonged it in both infarcted and intact zones. Astemizole was more effective than ebastine in prolonging the ERP and ventricular activation delay. Astemizole (0.3-3.0 mg/kg), but not ebastine, induced proarrhythmias in the PES-induced ventricular arrhythmia model. In conclusion, astemizole was proarrhythmic in the RT interval prolongation model while ebastine was not proarrhythmic in the canine myocardial infarcted heart.