EFFECT OF IBUTILIDE, A NEW CLASS-III AGENT, ON SUSTAINED ATRIAL-FIBRILLATION IN A CANINE MODEL OF ACUTE-ISCHEMIA AND MYOCARDIAL DYSFUNCTIONINDUCED BY MICROEMBOLIZATION

The effect of ibutilide, a new Class III antiarrhythmic agent, upon ac ute onset atrial fibrillation was investigated in a closed-chest canin e model of acute left ventricular (LV) dysfunction. Twenty-four anesth etized mongrel dogs, mean weight 24.9 +/- 4 kg were subjected to coron ary artery microsphere embolization and volume loading, followed by at tempted induction of atrial fibrillation (AF) by rapid atrial pacing. Acute ischemic LV dysfunction was successfully induced by embolization in all dogs, and caused significant (P < 0.02) decreases in LV systol ic pressure, peak + dp/dt (and - dp/dt), stroke volume, and RR interva l; whereas LV end diastolic pressure and QT(c) significantly increased . Sustained AF (greater-than-or-equal-to 30 min) was successfully indu ced in 15 of 24 dogs (62%) and unsustained AF (< 30 min) was induced i n the remainder (38%). At 30 minutes after induction of sustained AF, 15 dogs were randomized to intravenous ibutilide (0.15 mg/kg, given as a 0.075 mg/kg bolus, followed by 0.075 mg/kg infusion over 1 hour; n = 7) or placebo (saline; n = 8). There were no statistically significa nt differences between the ibutilide and the placebo groups with respe ct to mean LV systolic pressure, LV end diastolic pressure, LV dp/dt, RR interval, or QT(c) interval during AF prior to infusion. All seven dogs receiving ibutilide converted to sinus rhythm after a median of 3 minutes (range 0.5-26 min), while only three of eight placebo dogs (P < 0.03) converted to sinus rhythm after a median duration of 30 minut es (range 15-60 min) (P < 0.04 for difference in time to conversion). QT(c) prolonged by 27 +/- 17%, 1 hour after ibutilide, but was unalter ed after placebo (P less-than-or-equal-to 0.02). There were no signifi cant hemodynamic changes after either ibutilide or placebo. We conclud e that: (1) sustained AF (greater-than-or-equal-to 30 min) can be read ily induced in this closed-chest animal model and used to test antiarr hythmic agents acutely; and (2) intravenous ibutilide is effective in rapidly terminating acute onset AF; the drug prolongs the QT(c) interv al but does not exacerbate preexisting hemodynamic compromise in the a cutely ischemic LV.