ANTIARRHYTHMIC EFFECTS OF A NOVEL CLASS-III DRUG, KCB-328, ON CANINE VENTRICULAR ARRHYTHMIA MODELS

KCB-328 is a newly synthesized class III drug. To determine whether th is drug has antiarrhythmic or proarrhythmic effects, we used canine ve ntricular arrhythmia models Induced by coronary ligation and reperfusi on, programmed electrical stimulation (PES), two-stage coronary ligati on, digitalis, or epinephrine. KCB-328, in an intravenous infusion of 0.5 mg/kg/30 min, prolonged the QT(c) interval only 11%, but had antia rrhythmic effects on the reentry arrhythmias induced by PES (12 of 12 dogs with old myocardial infarction; p < 0.05). KCB-328, in an infusio n of 1 mg/kg/h, suppressed the occurrence of fatal ventricular fibrill ation (VF) induced by coronary ligation and reperfusion under either h alothane anesthesia (p < 0.05) or pentobarbital anesthesia (p < 0.05). Under the halothane anesthesia, KCB-328 alone showed proarrhythmic ef fects [i.e., induction of ventricular premature contractions (VPCs)], but it did not induce a more severe effect such as torsades de pointes -type ventricular tachycardia (VT). In addition, KCB-328 had weak anti arrhythmic effects on the automaticity arrhythmias induced by 24-h cor onary ligation but was effective neither on 48-h coronary ligation arr hythmias nor on the digitalis- and epinephrine-induced arrhythmias. Ou r results indicate that KCB-328 has powerful antiarrhythmic effects wi th fewer proarrhythmic potencies.