Bepridil significantly increased relative and effective refractory periods in normal and infarcted canine ventricular tissue (p<0.05-0.01) and reduced VT inducibility.
Does bepridil alter electrophysiologic properties and reduce ventricular tachycardia inducibility in infarcted canine myocardium?
Bepridil increases refractoriness and selectively delays conduction in ischemically injured tissue, contributing to its antiarrhythmic effects in a canine model of myocardial infarction.
p-value: p=<0.05-0.01
The electrophysiologic effects of bepridil, 10 mg/kg i.v., were determined in normal noninfarcted and in infarcted ventricular myocardium in 8 urethane-anesthetized dogs 4-6 days after anterior myocardial infarction. At drive cycle lengths of 400 and 333 ms, bepridil significantly increased relative (RRP) and effective (ERP) refractory periods in both normal ventricular tissue (mean increases, RRP 7-14%, ERP 5-6%, p less than 0.05-0.01) and in infarcted ventricular tissue (mean increases, RRP 12-15%, ERP 13-14%, p less than 0.01). Bepridil also selectively prolonged the local activation delay in infarcted ventricular myocardium (mean increases 37.5-45.1%, p less than 0.01), while ventricular excitation thresholds were not altered by bepridil in either normal or infarcted myocardium. Before bepridil administration, programmed ventricular stimulation initiated sustained ventricular tachycardias in 6 of the 8 postinfarction dogs tested. After bepridil, 2 of the 6 previously responsive animals were rendered noninducible, 3 animals responded to programmed stimulation with nonsustained tachyarrhythmias of relatively slower rates, and the one remaining dog responded with sustained ventricular tachycardia (VT). These data suggest that increases in refractoriness in both normal noninjured and in ischemically injured ventricular tissue, with a selective delay in conduction in ischemically injured tissue, contribute to the antiarrhythmic actions of bepridil in the setting of myocardial infarction.
Lynch et al. (1986) studied anterior myocardial infarction (n=8). Bepridil vs. baseline was evaluated on relative (RRP) and effective (ERP) refractory periods (p=<0.05-0.01). Bepridil significantly increased relative and effective refractory periods in normal and infarcted canine ventricular tissue (p<0.05-0.01) and reduced VT inducibility.