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.