辛伐他汀在正常及晚钠电流增大时对兔离体左室复极过程的影响  

In vitro effects of simvastatin on repolarization in rabbit left ventricular wedge preparations under normal circumstance and case of late I_(Na) augmenting

作　　者：王丹[1,2] 薛小临[1] 杨琳[1] 李佳娜[1] 严干新 王阿利 

机构地区：[1]西安交通大学第一附属医院心内科,教育部环境与疾病相关基因离子通道病重点实验室,陕西西安710061 [2]咸阳市中心医院心内科,陕西咸阳712000 [3]Main Line Health Heart Center,Wynnewood,PA 19096,USA

出　　处：《中国心脏起搏与心电生理杂志》2017年第3期251-254,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

摘　　要：目的观察辛伐他汀在正常及晚钠电流(INa-L)增大的情况下对离体兔左室心电活动的影响。方法建立经冠状动脉灌注兔左室楔形组织块标本。实验分为两部分:正常情况组:以自身空白作对照,依次给予10、30、100nmol/L浓度的辛伐他汀;INa-L增大组:使用海葵毒素(ATX-II)建立INa-L增大模型后,依次给予10、30、100nmol/L浓度的辛伐他汀。记录各组跨壁心电图及动作电位,观察QRS波宽度、QT间期、T波峰值至终点的时程(Tp-e)、Tp-e/QT及动作电位复极90%时程(APD90)在上述分组中的变化,以及是否引发早期后除极(EAD)和尖端扭转型室性心动过速(TdP)。结果 (1)在正常情况下,辛伐他汀在10、30、100nmol/L浓度下对QRS波宽度、QT间期、Tp-e间期、Tp-e/QT、APD90均无明显影响(P>0.05)。(2)INa-L增大后,10nmol/L辛伐他汀对上述电生理指标无明显影响(P>0.05),30nmol/L及100nmol/L辛伐他汀则显著延长QT间期和APD90(P<0.01),同时减小Tp-e/QT(P<0.05)。且未见EAD及TdP发生。结论在正常情况下,辛伐他汀对兔离体左室除极及复极活动无明显影响;INa-L增大后,高于治疗浓度的辛伐他汀可延长复极时程,同时显著减小跨壁复极离散度,从而降低致心律失常风险。Objective Observe the effect of simvastatin on electrical activity of rabbit heart in absence and pres ence of ATX-II, an enhancer of Late INa-L. Methods Established the arterially perfusing rabbit left ventricular wedge preparations and divided into two parts. In the normal group,we observed QRS duration, QT interval, Tp-e interval, APD＋0 and Tp-e/QT ratio in the absence and presence of treatment with simvastatin, and in the Late INa Augmenting group, we used ATX-Ⅱ to establish model hearts with Late INa augmenting and then measured those electrophysiological indicators in the absence and presence of treatment with simvastatin. Results In normal hearts, simvastatin at concentrations of 10,30,100 nmol/L had no significant effect on QRS complex, QT interval, Tp-e interval, APDg0 and Tp-e/QT ratio （n=6, P〉0.05）. In the presence of 3 nmol/L ATX-II, simvastatin （10 nmol/L） had no sitznificant effect on those electroohvsiological indicators,but significantlv prolonged OT interval and APDo.and decreased Tp-e/QT ratio at concentrations of 30 nmol/L and 100 nmol/L （n=7, P〈0.01）.No EADs and TdP occured. Conclusions Simvastatin has no significant effect on depolarization and repolarization activities in rabbit left ventricular wedge preparations. In hearts with INa-L augmenting, simvastatin at higher than therapeutic concentrations could prolong repolar- izationduration and increase left ventricular electrical stability, and thus reduces arrhythmogenic risks.

关 键 词：心血管病学 辛伐他汀 左室楔形标本 晚钠电流 跨壁复极离散度 

分 类 号：R331.38[医药卫生—人体生理学]