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

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Abstract
The effect of ibutiJide, a new Class III antiarrhythmic agent, upon acute onset atriai fibriJIation was investigated in a closed-chest canine model of acute left ventricular fLVj dysfunction. Twenty-four anesthetized mongrel dogs, mean weight 24.9 ± 4 kg were subjected to coronary artery microsphere emboiization and volume Joading, followed by attempted induction of atrial fihrillation (AF) by rapid atrial pacing. Acute ischemic LV dysfunction was successfully induced by emboiization in aii dogs, and caused significant (P < 0.02) decreases in LV systolic pressure, peak + dp/dt (and − dp/dtj, stroke volume, and RR interval; whereas LV end diastolic pressure and QTc significantiy increased. Sustained AF (≥ 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 ibutiiide (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 diastoJic pressure, LV dp/dt, RR intervaJ, or QTc intervaJ during AF prior to infusion. All seven dogs receiving ibutiJide converted to sinus rhythm after a median of 3 minutes (range 0.5–26 min), whiJe onJy three of eight pJacebo dogs (P < 0.03J converted to sinus rhythm after a median duration of 30 minutes (range 15–60 min) (P < 0.04 for difference in time to conversionj. QTc prolonged by 27 ± 17%, 1 hour after ibutiJide, but was unaJtered after pJacebo (P ≥ 0.02). There were no significant hemodynamic changes after either ibutiJide or pJacebo. We concJude that: (1) sustained AF (> 30 min) can be readily induced in this closed-chest animal model and used t o test antiarrhythmic agents acutely; and (2) intravenous ibutiJide is effective in rapidJy terminating acute onset AF; the drug prolongs the QTc intervaJ but does not exacerbate preexisting hemodynamic compromise in the acutely ischemic LV.