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

The effect of ibutilide, a new Class III antiarrhythmic agent, upon acute onset atrial fibrillation was investigated in a closed-chest canine model of acute left ventricular (LV) dysfunction. Twenty-four anesthetized mongrel dogs, mean weight 24.9 +/- 4 kg were subjected to coronary artery microsphere embolization and volume loading, followed by attempted 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 systolic pressure, peak + dp/dt (and - dp/dt), stroke volume, and RR interval; whereas LV end diastolic pressure and QT(c) significantly increased. Sustained AF (greater-than-or-equal-to 30 min) was successfully induced in 15 of 24 dogs (62%) and unsustained AF (< 30 min) was induced in 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 significant differences between the ibutilide and the placebo groups with respect 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 minutes (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 unaltered after placebo (P less-than-or-equal-to 0.02). There were no significant hemodynamic changes after either ibutilide or placebo. We conclude that: (1) sustained AF (greater-than-or-equal-to 30 min) can be readily induced in this closed-chest animal model and used to test antiarrhythmic agents acutely; and (2) intravenous ibutilide is effective in rapidly terminating acute onset AF; the drug prolongs the QT(c) interval but does not exacerbate preexisting hemodynamic compromise in the acutely ischemic LV.