辛伐他汀对血脂正常兔心肌缺血再灌注后瞬间外向钾通道电流的影响

目的： 观察辛伐他汀预处理对兔心肌缺血再灌注后瞬间外向钾通道电流（Ito）的影响，探讨他汀类药物抗心律失常的细胞学离子机制。方法: 45只新西兰大耳白兔随机分为3组：缺血再灌注动物模型组（I－R组，结扎冠脉左前降支30 min后再开放120 min）；辛伐他汀治疗组（他汀组，手术前给予辛伐他汀 5 mg·kg-1·d-1）；假手术对照组（只开胸不结扎血管）。采用酶解的方法分离缺血部位心室肌外膜单个心室肌细胞，应用全细胞膜片钳技术记录Ito，同时检测各组血脂水平。结果: 各组动物血脂水平无显著差异。Ito电流密度峰值（＋60 mV）显示：对照组为（17.41± 3.13）pA/pF(n=15)，I－R组为（9.49 ±1.91） pA/pF(n=11)，低于对照组（P＜0.01）。他汀组为（15.24 ± 2.41） pA/pF (n=11)，显著高于I－R组（P＜0.01），但仍明显小于对照组（P＜0.05）。另外，I－R组Ito失活曲线左移，失活后恢复时间延长，他汀组这些异常也明显恢复。结论: 本研究显示缺血再灌注可导致梗死区心肌细胞Ito明显下降，形成电重构，可引起心肌细胞动作电位延长，为再灌注心律失常的形成机制之一。辛伐他汀预处理可减轻Ito的异常变化，逆转电重构，而不依赖于降血脂效应，可能为他汀类药物降低心律失常发生率的细胞学离子机制。

Effects of simvastatin on transient outward potassium current in ventricular myocytes of normocholesterolemic rabbits suffering from ischemia and reperfusion

AIM: To investigate the effects of simvastatin on transient outward potassium current (Ito) in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the cellular (ionic) mechanism of statin treatment for antiarrhythmia. METHODS: Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (statin) and sham-operation control group (sham). Anesthetized rabbits were subjected to 30 min ischemia by ligation of the left anterior descending coronary artery and 60 min reperfusion after oral administration of simvastatin at dose of 5 mg·kg-1·d-1(statin group) or placebo (I-R group) for 3 d. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in I-R, statin group and the same anatomy region in sham. Whole cell patch clamp technique was used to record Ito. Simultaneously, the level of serum cholesterol was examined. RESULTS: No significant difference in serum cholesterol concentration among three groups was observed. The Ito current density (at +60 mV) was significantly decreased in I-R ［(9.49 ±1.91) pA/pF, n=11］ compared with sham ［(17.41± 3.13) pA/pF, n=15, P＜0.01］ and statin ［(15.24 ± 2.41) pA/pF, n=11, P＜0.01］, although there was slight reduction in statin group compared with sham (P＜0.05). CONCLUSION: Ischemia-reperfusion induces significant down-regulation of Ito, which may underlie the altered electrical activity and prolong abnormal transmembrane action potential duration of the surviving ventricular myocytes. Pretreatment with simvastatin attenuates these changes without lowering the serum cholesterol level, suggesting that simvastatin may reverse this electrical remodeling, thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.