1. This study was designed to determine whether
clofilium exhibits antifibrillatory activity in a
pinacidil +
hypoxia-induced model of
ventricular fibrillation (VF) in Langendorff-perfused hearts. 2. Ten minutes after exposure to vehicle or
clofilium (0.1, 1.0 and 10.0 microM), hearts were exposed to
pinacidil (1.25 microM), then subjected to 12 min of
hypoxia and reoxygenated. Onset to VF was recorded. Additional groups of hearts were pretreated with
UK-68,798 (1.0, 3.0 and 10.0 microM), a delayed rectifier channel blocker, and
5-hydroxydecanoate (10 microM), a known
ATP-dependent K+ channel blocker, and subjected to an identical protocol. 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 microM
clofilium. In addition,
5-hydroxydecanoate protected hearts from VF, while
UK-68,798 pretreatment did not. 4. In a separate group of hearts, electrically-induced VF was converted to sinus rhythm in 10/11 hearts after
clofilium was introduced as a bolus. 5.
Clofilium is capable of preventing VF in the rabbit isolated heart in a concentration-dependent manner. We have data to suggest that the ability of
clofilium to attenuate the effects of pinacidil+hypoxia in our model may include blockade of metabolically active K+ channels, i.e., KATP (
glibenclamide-sensitive) channel.