EFFECT OF QUINIDINE AND SOTALOL ON QT INTERVAL AND HEART RATE IN MINIATURE SWINE

摘要

Drug-induced QT prolongation is a major clinical risk factor for arrhythmia induction. Preclinical examinations of effect on QT interval and ventricular repolarization have become important for the safety assessment of new pharmaceuticals. Although drug-related changes on the QT interval tend to be species specific, the characteristics of drug-induced changes in the QT interval in miniature swine were still unknown. Therefore, the purpose of this study was to determine the effects of quinidine and sotalol in miniature swine, known to prolong the QT interval in other animal species in vivo. Electrocardiogram was recorded for 24-h periods using a telemetry system. Each miniature swine was treated with vehicle, quinidine (5.0 mg/kg, i.v.), and sotalol (2.5 mg/kg, i.v.). Sotalol produced the QT prolongation and bradycardia. Quinidine also induced the QT prolongation, but heart rate showed biphasic phenomenon; initially increased and later decreased. Moreover, the QT/RR relationship in both drugs exhibited "reverse rate dependence", a characteristic which has been described in multicellular in vitro preparations. These results suggest that miniature swine may be useful preclinical species for cardiovascular safety assessment of new pharmaceuticals.