抄録
Background: Because bepridil blocks multiple myocardial ionic channels, including the muscarinic acetylcholine receptor-operated potassium current (IKAch), bepridil is expected to suppress atrial fibrillation (AF) mediated by vagal nerve stimulation (VNS). Methods and Results: The therapeutic effects of bepridil were studied with a special focus on heart rate variability (HRV) in a canine model of AF. During VNS, AF was induced in 9 of 9 experiments before, vs 3 of 9 experiments after administration of bepridil (P<0.01). During 350 ms atrial pacing, VNS shortened the right and left atrial monophasic action potentials at 90% repolarization (MAP90) by -31±8% and -22±12%, respectively, vs -10±13% and -6±8%, respectively, after bepridil (P<0.01, N=9). Bepridil prolonged the sinus cycle length, although it had no significant effect on the conduction time measured at 300 ms pacing. Statistically insignificant change was observed in the VNS-induced slowing of the sinus cycle length and in the VNS-induced increase in high frequency amplitude of HRV before (1.2±0.7 to 5.3±4.0 ms) vs after (1.7±0.8 to 5.4±2.3 ms) bepridil administration. Conclusions: Bepridil prevented the VNS-induced shortening of atrial MAP90 and suppressed the inducibility of AF during VNS in two-thirds of the experiments. As far as this study shows, it may be possible that inhibition of IKAch played a part in this antifibrillatory effect.
