ANTIARRHYTHMIC AND ELECTROPHYSIOLOGIC EFFECTS OF IBUTILIDE IN A CHRONIC CANINE MODEL OF ATRIAL-FLUTTER

We studied the effects of orally administered ibutilide, a class III a ntiarrhythmic agent, in a model of reentrant atrial flutter in conscio us dogs. After baseline determination of atrial effective refractory p eriod (AERP) and demonstration of reproducible induction of atrial flu tter by rapid atrial pacing, 8 dogs received either placebo or one of six doses of ibutilide ranging from 0.1 to 5 mg/kg. Refractory periods and the ability to induce atrial flutter were then assessed at period ic intervals for 8 hours. Ibutilide produced dose-related increases in AERP which were well correlated with prevention of initiation of atri al flutter after doses greater-than-or-equal-to 0.25 mg/kg. Placebo an d 0.1 mg/kg ibutilide had no effect on AERP or the ability to induce a trial flutter. Doses of 0.25 to 1.0 mg/kg ibutilide significantly incr eased AERP and prevented induction of atrial flutter for 4-6 h. After treatment with 2.5 or 5 mg/kg ibutilide, significant increases in AERP and prevention of induction of atrial flutter persisted throughout th e 8-h study period. The cycle length of inducible atrial flutter was s ignificantly increased after administration of 5 mg/kg ibutilide. The results demonstrate oral efficacy of ibutilide with rapid onset of act ion (in 30-60 min), resulting in increased AERP and prevention of indu ced atrial flutter in this model.