title: Bepridil enhances aprindine-induced prolongation of atrial effective refractory period in a canine atrial rapid pacing model.
abstract: BACKGROUND
  Bepridil in combination with aprindine could restore sinus rhythm in patients with persistent atrial fibrillation (AF). The present study aimed to investigate the electrophysiological mechanisms of the combined effects of bepridil and aprindine.
  
  
  METHODS
  Subjects consisted of 6 dogs without and 6 dogs with atrial rapid pacing (ARP) carried out at 400 bpm for 2 weeks. Bepridil was administered for 1 week in both groups (ARP dogs were administered bepridil in the second week). The electrophysiological effects of the intravenous administration of aprindine (1mg/kg) were evaluated before and after the administration of bepridil.
  
  
  RESULTS
  In non-paced dogs, the atrial effective refractory period (AERP) became longer after the administration of bepridil (from 151±10 ms to 170±7 ms, p<0.05); however, no additional AERP prolongation was observed after the acute administration of aprindine. In ARP dogs, the AERP shortened with ARP for a week, and tended to lengthen after the administration of bepridil (from 93±5 ms to 118±9 ms, p=0.08). In these dogs, the acute aprindine administration did not prolong the AERP before the administration of bepridil, although it did after the administration of bepridil (from 118±9 ms to 142±8 ms, p<0.01). AF duration did not change after the administration of bepridil, although it shortened significantly after the additional administration of aprindine (from 2.2±0.3s to 1.4±0.8s, p<0.05).
  
  
  CONCLUSIONS
  Bepridil enhances the effect of aprindine for the prevention of AF by reversing atrial electrical remodeling.
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan. Electronic address: knishida@med.u-toyama.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Division of Cardiology, Shizuoka Red Cross Hospital, Shizuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Sakabe
authors.affiliation: Division of Cardiology, Shizuoka Red Cross Hospital, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujiki
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizumaki
authors.affiliation: Second Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001073:Aprindine / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000662:veterinary; D016275:Atrial Function / Q000187:drug effects*; D064752:Atrial Remodeling / Q000187:drug effects; D015764:Bepridil / Q000008:administration & dosage*; D004285:Dogs; D004359:Drug Therapy, Combination / Q000379:methods; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D001073:Aprindine; D015764:Bepridil
keywords: Aprindine; Atrial fibrillation; Atrial remodeling; Bepridil