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 myo cardial 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 afte r two-stage coronary artery ligation as described by Harris. RS-2135 ( 1.25 and 2.5 mg/kg intravenously, i.v.) suppressed sustained ventricul ar tachycardia (SVT) 24 h after coronary embolization in the bead mode l. The antiarrhythmic effects of i.v. administration of RS-2135 were m ore 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 e ffects of oral (p.o.) administration of RS-2135 were evaluated 48 h af ter coronary embolization. RS-2135 (10 mg/kg p.o.) was equipotent to f lecainide (10 mg/kg p.o.) and twice as potent as disopyramide (20 mg/k g p.o.) and mexiletine (20 mg/kg p.o.). Onset of antiarrhythmic effect s after p.o. RS-2135 was slower than that of other drugs. These data s uggest that the bead model is as useful as the Harris model for evalua tion of the antiarrhythmic potential of chemicals and that RS-2135, ei ther i.v. or p.o., is effective against SVT after acute MI.