Ohashi Narutaka, Mitamura Hideo, Tanimoto Kojiro, Fukuda Yukiko, Kinebuchi Osamu, Kurita Yasuo, Shiroshita-Takeshita Akiko, Miyoshi Shunichiro, Hara Motoki, Takatsuki Seiji, Ogawa Satoshi
Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
J Cardiovasc Pharmacol. 2004 Sep;44(3):386-92. doi: 10.1097/01.fjc.0000138163.11612.7b.
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.
钙超载在心房电重构的发生发展中起关键作用。据报道,L型钙通道阻滞剂预防这种重构的效果持续时间较短,部分原因是该通道下调以及通过T型钙通道持续有钙内流。为了证明L型和T型双钙通道阻滞剂依福地平是否比L型钙通道阻滞剂维拉帕米具有更大的作用,对21只犬以400次/分钟的频率进行快速心房起搏14天,其中7只犬(E组)用依福地平预处理,7只犬(V组)用维拉帕米预处理,7只犬(C组)不做预处理。在快速起搏的14天期间连续测量心房有效不应期(ERP)。在快速起搏时,C组的ERP逐渐降低。相反,在第2至7天,E组和V组的ERP仍高于C组(P<0.01)。然而,在第14天,V组的ERP降至C组的水平,而E组的ERP仍显著长于C组或V组的ERP(P<0.01)。单独阻断L型钙通道是不够的,但加用T型钙通道阻滞剂对预防心房电重构具有更持久的作用。