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Bepridil Reverses Atrial Electrical Remodeling and L‐Type Calcium Channel Downregulation in a Canine Model of Persistent Atrial Tachycardia
Author(s) -
NISHIDA KUNIHIRO,
FUJIKI AKIRA,
SAKAMOTO TAMOTSU,
IWAMOTO JOTARO,
MIZUMAKI KOICHI,
HASHIMOTO NORIO,
INOUE HIROSHI
Publication year - 2007
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2007.00833.x
Subject(s) - bepridil , medicine , effective refractory period , atrial fibrillation , cardiology , atrial tachycardia , tachycardia , anesthesia , placebo , endocrinology , calcium , catheter ablation , pathology , verapamil , alternative medicine
This study tested whether bepridil, a multichannel blocker, would reverse electrical remodeling induced by persistent atrial tachycardia. Methods and Results: Fourteen dogs were subjected to rapid atrial pacing at 400 bpm for 6 weeks after atrioventricular block was created to control the ventricular rate. During the study period, seven dogs were given placebo for 6 weeks (Control group), and seven were given placebo for 3 weeks, followed by 3 weeks of bepridil (10 mg/kg/day, Bepridil group). The atrial effective refractory period (ERP) and the inducibility and duration of atrial fibrillation (AF) were determined on a weekly basis. After 6 weeks, expression of L‐type calcium channel α 1C messenger ribonucleic acid (mRNA) was quantified by real‐time reverse transcription‐polymerase chain reaction. In the Control group, ERP was shortened and the inducibility and duration of AF increased through the 6‐week period. In the Bepridil group, the same changes occurred during the first 3 weeks, but were gradually reversed with bepridil. After 6 weeks, ERP was longer, AF inducibility was lower, and AF duration was shorter in Bepridil group than in the Control group. Expression of α 1C mRNA was decreased by 64% in the Control group (P < 0.05 vs sham), but in the Bepridil group, it was not different compared with the sham dogs. As a whole group of dogs, ERP was positively correlated with α 1C mRNA expression. Conclusion: Bepridil reverses the electrophysiological consequences of atrial remodeling to some extent and L‐type calcium channel downregulation in a canine model of atrial tachycardia.