Bepridil reverses atrial electrical remodeling and L-type calcium channel downregulation in a canine model of persistent atrial tachycardia.
BACKGROUND
This study tested whether bepridil, a multichannel blocker, would reverse electrical remodeling induced by persistent atrial tachycardia.


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.


CONCLUSIONS
Bepridil reverses the electrophysiological consequences of atrial remodeling to some extent and L-type calcium channel downregulation in a canine model of atrial tachycardia.
Nishida
Kunihiro
K
Second Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan.
Fujiki
Akira
A
Sakamoto
Tamotsu
T
Iwamoto
Jotaro
J
Mizumaki
Koichi
K
Hashimoto
Norio
N
Inoue
Hiroshi
H
D000818:Animals; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology; D015764:Bepridil / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013612:Tachycardia, Ectopic Atrial / Q000188:drug therapy* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D012333:RNA, Messenger; D015764:Bepridil