ANTIFIBRILLATORY EFFECTS OF CLOFILIUM IN THE RABBIT ISOLATED HEART

1 This study was designed to determine whether clofilium exhibits anti fibrillatory activity in a pinacidil + hypoxia-induced model of ventri cular fibrillation (VF) in Langendorff-perfused hearts. 2 Ten minutes after exposure to vehicle or clofilium (0.1, 1.0 and 10.0 mu M), heart s were exposed to pinacidil (1.25 mu M), then subjected to 12 min of h ypoxia and reoxygenated. Onset to VF was recorded. Additional groups o f hearts were pretreated with UK-68,798 (1.0, 3.0 and 10.0 mu M), a de layed rectifier channel blocker, and 5-hydroxydecanoate (10 mu M), a k nown ATP-dependent K+ channel blocker, and subjected to an identical p rotocol. 3 Clofilium decreased the incidence of VF in a concentration- dependent manner; 7/9 control hearts developed VF vs 1/9 hearts (P = 0 .007, Fisher's Exact) treated with 10.0 mu M clofilium. In addition, 5 -hydroxydecanoate protected hearts from VF, while UK-68,798 pretreatme nt did not. 4 In a separate group of hearts, electrically-induced VF w as converted to sinus rhythm in 10/11 hearts after clofilium was intro duced as a bolus. 5 Clofilium is capable of preventing VF in the rabbi t isolated heart in a concentration-dependent manner. We have data to suggest that the ability of clofilium to attenuate the effects of pina cidil + hypoxia in our model may include blockade of metabolically act ive K+ channels, i.e., K-ATP (glibenclamide-sensitive) channel.