Narutaka Ohashi

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.

Development of newer calcium channel antagonists: therapeutic potential of efonidipine in preventing electrical remodelling during atrial fibrillation.

Calcium channel antagonists are most frequently prescribed for the treatment of hypertension and the majority specifically inhibit the L-type Ca2+ channel. In order to prevent reflex sympathetic over activity caused by L-type calcium channel antagonists (calcium channel blockers [CCBs]), increasing attention has focused on the blockade of the T-type Ca2+ channel. The T-type Ca2+ channel is found in the kidney and can also appear in the ventricle of the heart when in failure. Therefore, the T-type Ca2+ channel is a possible new target for the treatment of nephropathy and heart failure. In clinical trials, the efficacy and safety of T-type CCBs in hypertension and chronic renal disease have been reported.It is well known that the T-type Ca2+ channel is present in the adult atrium and plays a role in the cardiac pacemaker, but recent experimental studies suggest that this current also promotes electrical remodelling of the atrium. Using efonidipine, a dual L- and T-type CCB, it has been demonstrated that atrial electrical remodelling can be diminished in dogs. Furthermore, the T-type Ca2+ channel has recently been found in the pulmonary veins, contributing to the pulmonary vein pacemaker activity and triggered activity. A variety of drugs having T-type CCB effects have been shown to be effective in the management of atrial fibrillation, suggesting that this channel may be a novel therapeutic target.