Effects of RS-2135, a novel class I antiarrhythmic agent, on sustained ventricular tachycardia after coronary embolization in conscious dogs

To assess the ability of RS-2135, a novel class I antiarrhythmic agent to suppress ischemia-induced ventricular arrhythmias, we produced myocardial infarction (MI) by introducing a glass bead into the coronary artery of the dog (bead model). Ventricular arrhythmias after coronary embolization were as severe and long-lasting as those that occur after two-stage coronary artery ligation as described by Harris. RS-2135 (1.25 and 2.5 mg/kg intravenously, i.v.) suppressed sustained ventricular tachycardia (SVT) 24 h after coronary embolization in the bead model. The antiarrhythmic effects of i.v. administration of RS-2135 were more potent and more long-lasting than those of lidocaine (5 and 10 mg/kg i.v.), mexiletine (5 and 10 mg/kg i.v.), disopyramide (2.5 and 5 mg/kg i.v.), and flecainide (2.5 and 5 mg/kg i.v.). The antiarrhythmic effects of oral (p.o.) administration of RS-2135 were evaluated 48 h after coronary embolization. RS-2135 (10 mg/kg p.o.) was equipotent to flecainide (10 mg/kg p.o.) and twice as potent as disopyramide (20 mg/kg p.o.) and mexiletine (20 mg/kg p.o.). Onset of antiarrhythmic effects after p.o. RS-2135 was slower than that of other drugs. These data suggest that the bead model is as useful as the Harris model for evaluation of the antiarrhythmic potential of chemicals and that RS-2135, either i.v. or p.o., is effective against SVT after acute MI.