Antiarrhythmic effects of HOE642, a novel Na +-H + exchange inhibitor, on ventricular arrhythmias in animal hearts

HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na +-H + exchange subtype 1 inhibitor, was investigated for its possible antiarrhythmic effects on coronary artery ligation/reperfusion and ouabain-induced arrhythmias in the canine heart which may occur after intracellular Ca 2+ overload. Also, the effects of HOE642 on coronary artery ligation/reperfusion of the left coronary artery were tested in rat hearts. HOE642 (1 mg/kg) significantly suppressed the occurrence of fatal ventricular fibrillation during coronary artery ligation and after reperfusion in dogs (2 out of 8 dogs in the treated group compared to 7 out of 8 dogs in the control group, P