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Antifibrillatory effects of clofilium in the rabbit isolated heart
Author(s) -
Friedrichs Gregory S.,
Chi Liguo,
Green Alysia L.,
Lucchesi Benedict R.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16195.x
Subject(s) - pinacidil , glibenclamide , cardiology , medicine , hypoxia (environmental) , pharmacology , ventricular fibrillation , channel blocker , sinus rhythm , anesthesia , chemistry , atrial fibrillation , endocrinology , calcium , oxygen , organic chemistry , diabetes mellitus
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 μ m ), hearts were exposed to pinacidil (1.25 μ m ), 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 μ m ), a delayed rectifier channel blocker, and 5‐hydroxydecanoate (10 μ m ), 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 μ m 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., K ATP (glibenclamide‐sensitive) channel.