A comparison between calcium channel blocking drugs with different potencies for T- and L-type channels in preventing atrial electrical remodeling.
Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.
Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. narutaka@cpnet.med.keio.ac.jp
Narutaka
N
Ohashi
Hideo
H
Mitamura
Kojiro
K
Tanimoto
Yukiko
Y
Fukuda
Osamu
O
Kinebuchi
Yasuo
Y
Kurita
Akiko
A
Shiroshita-Takeshita
Shunichiro
S
Miyoshi
Motoki
M
Hara
Seiji
S
Takatsuki
Satoshi
S
Ogawa
D000284:Administration, Oral; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control*; D001283:Atrioventricular Node / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002304:Cardiac Pacing, Artificial / Q000379:methods; D004095:Dihydropyridines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004594:Electrophysiology; D005544:Forecasting; D006325:Heart Atria / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D007564:Japan; D008297:Male; D009596:Nitrophenols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D012107:Research Design; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D014700:Verapamil; D002118:Calcium