钾通道开放剂对长QT综合征LQT2模型的跨壁复极离散作用的实验研究

EFFECTS OF PINACIDIL ON TRANSMURAL DISPERSION OF REPOLARIZATION IN CANINE LEFT VENTRICLE IN LQT2 MODEL

目的观察钾通道开放剂(吡那地尔)对LQT2模型心室肌细胞动作电位时程(APD)及跨壁复极离散(TDR)的作用及电生理变化的影响,为临床治疗LQT2的药物选择提供理论基础。方法采用标准玻璃微电极技术,以d-索他洛尔(Ikr阻断剂)模拟LQT2模型。结果d-索他洛尔(100μmol/L)使三层心肌细胞APD90均增加,但以M细胞APD80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(2-6μmol/L)呈浓度依赖性地缩短受d-索他洛尔影响而延长的三层细胞的APD,以M细胞为著,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LQTs,钾通道开放剂可能有治疗作用。

Objective To investigate the effect of d - sotalol (Ikr blocker)on APD90 and transmural dispersion of repolarization(TDR) in endocardium, epicardium, M cells and the reversal effect of potassium channel opener (pinacidil). Methods We modeled LQT2 model by using standard glass micro-electrode method. Results It is shown that ① Superfused with d-sotalol(100mol/L), APD90 were prolonged in all three type cells, but most remarkable in M cells. TDR was markedly increased. Early afterdepolarizations (EADs) and APD alternant were induced by d - sotalol in M cells but they were not found in endocardinm and epicardium. ② In the presence with d ?sotalol, pinacidil (2 to 6mol/L) dose - dependent reversed the effects of d - sotalol on APD and TDR , and effectively eliminated EAD, APD alternant induced by d - sotalol. Conclusion Potassium channel openers might do some therapeutical effects on LQTs introduced by Ikr blocker.