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 -.
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.
Iijima
Kenichi
K
The First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan.
Chinushi
Masaomi
M
Izumi
Daisuke
D
Ahara
Shizue
S
Furushima
Hiroshi
H
Komura
Satoru
S
Hosaka
Yukio
Y
Sanada
Akiko
A
Sato
Akinori
A
Aizawa
Yoshifusa
Y
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
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D015764:Bepridil