title: Effect of bepridil in atrial fibrillation inducibility facilitated by vagal nerve stimulation. - Prevention of vagal nerve activation-induced shortening of the atrial action potential duration -.
abstract: BACKGROUND
  Because bepridil blocks multiple myocardial ionic channels, including the muscarinic acetylcholine receptor-operated potassium current (I(KAch)), bepridil is expected to suppress atrial fibrillation (AF) mediated by vagal nerve stimulation (VNS).
  
  
  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 I(KAch) played a part in this antifibrillatory effect.
authors.affiliation: The First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Iijima
authors.forename: Masaomi
authors.initials: M
authors.lastname: Chinushi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Izumi
authors.forename: Shizue
authors.initials: S
authors.lastname: Ahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furushima
authors.forename: Satoru
authors.initials: S
authors.lastname: Komura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Sanada
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D015764:Bepridil / Q000494:pharmacology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D009206:Myocardium; D055536:Vagus Nerve Stimulation
chemical_list: D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D015764:Bepridil