Inhomogenic Effect of Bepridil on Atrial Electrical Remodeling in a Canine Rapid Atrial Stimulation Model

作者：Hidehira Fukaya, Shinichi Niwano, Daisuke Satoh, Y Masaki, Hiroe Niwano, Jisho Kojima, Masahiko Moriguchi, Tohru Izumi · 发表于：Circulation Journal · 年份：2008 · DOI：10.1253/circj.72.318 · 被引用次数：25 · 研究领域：Cardiac electrophysiology and arrhythmias、Atrial Fibrillation Management and Outcomes、Ion channel regulation and function

BACKGROUND: The antiarrhythmic or reverse remodeling effects of bepridil, a multi-ion channel blocker, have been recently reported, but inhomogeneity of the electrical remodeling and effects of bepridil have been observed in previous reports. In this study, the effect of long-term administration of bepridil on atrial electrical remodeling was evaluated in a comparison of the right and left atrium (RA and LA) in a canine rapid atrial stimulation model. METHODS AND RESULTS: In 10 beagle dogs, rapid atrial pacing (400 beats/min) was delivered for 6 weeks and the atrial effective refractory period (AERP), conduction velocity (CV) and inducibility of atrial fibrillation (AF) were evaluated every week. In 5 of the pacing dogs, bepridil (10 mg . kg(-1) . day(-1)) was administered orally, starting 2 weeks after the initiation of the rapid pacing. At the end of the protocol, the hemodynamic parameters and extent of tissue fibrosis were evaluated and the mRNA of SCN5A, Kv4.3, the L-type Ca2+ channel (LCC) and connexin (Cx) 40, 43, and 45 in both atria were examined by quantitative real-time reverse transcriptase-polymerase chain reaction. In the pacing control group, AERP shortening, decreased CV, increased AF inducibility and downregulation of the expression of SCN5A and LCC were observed. In the bepridil group, the AERP exhibited a relatively quick recovery after bepridil was started in the first week and continued to recover gradually until the end of the protocol, but that recovery...