咪达普利对陈旧性心肌梗死非梗死区心肌跨室壁复极离散度及短暂外向钾电流的影响

The effects of imidapril on transmural dispersion of repolarization and transient outward potassium current three months after myocardial infarction

目的 探讨咪达普利对陈旧性心肌梗死非梗死区心肌跨室壁复极离散度（TDR）以及短暂外向钾电流（Ito）的影响。方法24只兔随机分为3组,两组结扎左冠状动脉回旋支制成心肌梗死模型,手术后1周1组给予咪达普利 0.625mg·kg-1·d-1口服（咪达普利组）,另1组则给予安慰剂口服（陈旧性心肌梗死组）;第3组开胸但不结扎冠状动脉也给予安慰剂口服（假手术组）。3个月后酶解分离得到左心室壁远离梗死中心区的3层心肌单细胞（心外膜下心肌细胞、中层心肌细胞和心内膜下心肌细胞）,用膜片钳技术研究跨室壁复极离散度（TDR）以及3层心肌细胞的短暂外向钾电流（Ito）的改变。结果 心肌梗死后3个月,非梗死区的心肌细胞发生了肥厚和重构,3层心肌细胞的动作电位时限（APD）明显延长,其中心内膜下心肌细胞的APD明显短于心外膜下心肌细胞和中层心肌细胞（P<0.01）,与假手术组对比呈相反的跨室壁离散。陈旧性心肌梗死TDR也明显增加,但TDR在咪达普利组和假手术组间差异不明显。陈旧性心肌梗死3层心肌细胞的Ito密度均降低,以心外膜下心肌细胞和中层心肌细胞较明显（P<0.05）,咪达普利组和假手术组相比,Ito密度无明显改变（P>0.05）。结论陈旧性心肌梗死远离梗死中心区的左心室心肌细胞发生代偿性肥厚,APD延长,TDR增加。

Objective The aim of this study is to investigate the effects of imidapril on transmural dispersion of repolarization and heterogeneous changes of transient outward potassium current in the region remote from the infarction area three months after myocardial infarction. Methods Twenty-four rabbits with both sex were randomly separated into 3 groups. OMI group underwent left circumflex coronary artery ligation and were fed with placebo, Imidapril group were similar but fed with imidapril 0.625 mg-kg-1-d-1,sham group underwent left thoracotomy with no coronary artery ligation and were fed with placebo. Three months later, the single myocytes were enzymatically isolated from the epimyocardium (Epi)、midmyocardium (M) and endomyocardium (Endo) in the free wall of left ventricle remote from the infarction area and the whole cell patch clamp technique was used to measure the action potential duration (APD) and Ito density. Results It is found that myocytes remote from the infarction area were hypertrophied and remodeled, the APD of all three layers of myocyte were lengthened, while the APD of Endo was shorter than that of Epi or M cell (P < 0.01).TDR was increased in OMI group than that of imidapril group and sham group (288. 32 ± 19.56) ms, (228.45± 13.94) ms, (210.32± 17.43) ms,respectively (P<0.01). Ito density in all three layers of myocytes were decreased after myocardial infarction, and the reduction was greater in M cell [ from (31.63 ± 3.13)pA.pF-1 to (20.74 ± 3.12)pA..pF-1, decreased 34.79%]than Epi [from(28.18± 2.34)pA. pF-1 to (20.46±1.48)pA.pF-1 decreased 29.76%] and Endo[from(10.53 ±2.52)pA.pF-1 to (8.41 ±0.58)pA. pF-1 decreased 21.56%].There was no significant difference between the sham group and imidapril group. Conclusion Myocytes remote from the infarction area 3 months after myocardial infarction had developed hypertrophy and remodeling. Imidapril could regress the left ventricular hypertrophy, increase Ito density, restore the dispersion of repolarization and decrease the vulnerability to induce ventricular arrhythmia.