Bepridil reverses atrial electrical remodeling and L-type calcium channel downregulation in a canine model of persistent atrial tachycardia.

Autor: Nishida K; Second Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan., Fujiki A, Sakamoto T, Iwamoto J, Mizumaki K, Hashimoto N, Inoue H
Jazyk: angličtina
Zdroj: Journal of cardiovascular electrophysiology [J Cardiovasc Electrophysiol] 2007 Jul; Vol. 18 (7), pp. 765-72. Date of Electronic Publication: 2007 Apr 30.
DOI: 10.1111/j.1540-8167.2007.00833.x
Abstrakt: Introduction: 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 alpha1C 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 alpha1C 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 alpha1C 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.
Databáze: MEDLINE
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