钾通道开放剂与钙拮抗剂对长QT综合征LQT2模型的跨壁复极离散的作用

采用标准玻璃微电极技术 ,以d 索他洛尔 (Ikr阻断剂 )模拟长QT 2型 (LQT2 )模型观察其对犬心室肌细胞动作电位复极 90 %时程 (APD90 )及跨壁复极离散 (TDR)的作用 ,及钾通道开放剂 (吡那地尔 )和钙通道阻断剂 (硝苯地平 )对d 索他洛尔诱发的电生理变化的影响 ,为临床治疗LQT2的药物选择提供理论基础。结果 :d 索他洛尔 (10 0μmol/L)使三层心肌细胞APD90 均增加 ,但以中层心肌 (M)细胞APD90 增加最为显著 ,结果使TDR增加。d 索他洛尔作用于M细胞 ,诱发早期后除极 (EADs)和APD交替变异 ,而心内膜、外膜细胞则未见。吡那地尔 (2～ 6 μmol/L)和硝苯地平 (2～ 10 μmol/L)均呈浓度依赖性地缩短受d 索他洛尔而延长的三层细胞的APD ,以M细胞最为显著 ,因此明显降低TDR ,并且消除d 索他洛尔所产生的EADs及APD交替变异。结论 :对于Ikr缺陷所致的长QT综合征 ,钾通道开放剂和钙通道阻断剂可能有治疗作用。

Effects of Pinacidil and Nifedipine on Transmural Dispersion of Repolarization in Canine Left Ventricle in Long QT2 Model.

.To observe the effects of d sotalol (Ikr blocker)on APD 90 and transmural dispersion of repolarization(TDR) in endocardium,epicardium,and M cells and the reversal effects of potassium channel opener (pinacidil),cacium channel blocker (nifedipine) by using standard glass microelectrode method.The results:①Superfusion with d sotalol(100 μmol/L),APD 90 were prolonged in all three type cells,but significantly in M cells.TDR was markedly increased.Early afterdepolarizations (EADs),APD alternans induced by d sotalol in M cells but not in endocardinm and epicardium.②In the presence with d sotalol,pinacidil(2 to 6 μmol/L) and nifedipine(2 to 10 μmol/L) dose dependently reversed the effects of d sotalol on APD and TDR,and effectively abolished EADs,APD alternans induced by d sotalol.