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

Abstract

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.

• Authors: Kunihiro Nishida, Akira Fujiki, Tamotsu Sakamoto, Jotaro Iwamoto, Koichi Mizumaki, Norio Hashimoto, Hiroshi Inoue
• Journal: Journal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 18 Issue 7 Pg. 765-72 (Jul 2007) ISSN: 1540-8167 [Electronic] United States
• PMID: 17472715 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Calcium Channels, L-Type
• L-type calcium channel alpha(1C)
• RNA, Messenger
• Bepridil

Topics

• Animals
• Atrial Function (drug effects, physiology)
• Bepridil (pharmacology, therapeutic use)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Calcium Channels, L-Type (biosynthesis, genetics, metabolism, physiology)
• Disease Models, Animal
• Dogs
• Down-Regulation (drug effects, physiology)
• RNA, Messenger (antagonists & inhibitors, biosynthesis)
• Tachycardia, Ectopic Atrial (drug therapy, physiopathology)
• Up-Regulation (drug effects, physiology)