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J Cardiovasc Pharmacol ; 44(3): 386-92, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15475838

ABSTRACT

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.


Subject(s)
Atrial Fibrillation/prevention & control , Atrioventricular Node/drug effects , Atrioventricular Node/physiopathology , Calcium Channel Blockers/pharmacokinetics , Calcium Channels, L-Type/drug effects , Calcium Channels, T-Type/drug effects , Administration, Oral , Animals , Atrial Fibrillation/physiopathology , Atrioventricular Node/anatomy & histology , Calcium/antagonists & inhibitors , Calcium/metabolism , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/therapeutic use , Calcium Channels, L-Type/pharmacokinetics , Calcium Channels, L-Type/therapeutic use , Calcium Channels, T-Type/pharmacokinetics , Calcium Channels, T-Type/therapeutic use , Cardiac Pacing, Artificial/methods , Dihydropyridines/administration & dosage , Dihydropyridines/chemistry , Dihydropyridines/pharmacokinetics , Dogs , Electrophysiology , Forecasting , Heart Atria/anatomy & histology , Heart Atria/drug effects , Heart Atria/physiopathology , Japan , Male , Nitrophenols/administration & dosage , Nitrophenols/chemistry , Nitrophenols/pharmacokinetics , Organophosphorus Compounds/administration & dosage , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacokinetics , Refractory Period, Electrophysiological/drug effects , Refractory Period, Electrophysiological/physiology , Research Design , Time Factors , Verapamil/administration & dosage , Verapamil/pharmacokinetics
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