ANTIFIBRILLATORY EFFECTS OF IBUTILIDE IN THE RABBIT ISOLATED HEART - MEDIATION VIA ATP-DEPENDENT POTASSIUM CHANNELS

This study determined if ibutilide, a drug with class III activity, ex hibited antifibrillatory effects in an isolated heart model of ventric ular fibrillation (VF). Langendorff-perfused hearts were randomized am ong six groups. Group I (n = 9) served as the vehicle-treated control group. Groups II (n = 6), III (n = 10) and IV (n = 9) were pretreated with ibutilide 0.1; 1.0 or 3.0 muM, respectively. Ten minutes after pe rfusion in the presence of vehicle or ibutilide, hearts were perfused with the ATP-dependent potassium channel opener, pinacidil (1.25 muM) and subjected to a 12-min hypoxic period followed by 40 min of reoxyge nation, or until the onset of VF. Groups V and VI were used to investi gate electrophysiological effects of ibutilide (n = 12), as well as it s chemical defibrillatory activity (n = 9), respectively. Additional e xperiments involved isometric tension recordings from canine atrial pe ctinate muscle exposed to increasing concentrations of pinacidil (3-30 0 muM) in the presence of ibutilide (3-30 muM). lbutilide decreased th e incidence of VF in a concentration-dependent manner; eight of nine c ontrol hearts developed VF vs. two of nine hearts (P = .01 8 chi2) tre ated with 3.0 muM ibutilide. In atrial pectinate tissue, ibutilide att enuated the negative inotropic effect of pinacidil. An unexpected find ing was the ability of ibutilide to achieve chemical defibrillation wh en added to the perfusion medium after the electrical induction of ven tricular fibrillation in the isolated heart. The antifibrillatory effe ct of ibutilide may result from inhibition of the ATP-dependent potass ium channel made susceptible to opening by pinacidil during hypoxia.