I_(Ks)复极储备下调对心肌肥厚豚鼠室性心律失常发生的影响  

Effect of down-regulation of I_(Ks) repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy

作　　者：汪和贵[1] 黄霆 王政 葛楠楠 柯永胜[1] WANG Hegui;HUANG Ting;WANG Zheng;GE Nannan;KE Yongsheng(Department of Cardiology, Yijishan Hospital of Wannan Medical College, Wuhu Anhui 241001, China)

机构地区：[1]皖南医学院附属弋矶山医院心血管内科,安徽芜湖241001

出　　处：《中南大学学报（医学版）》2018年第4期428-433,共6页Journal of Central South University ：Medical Science

基　　金：安徽省自然科学基金(1308085MH116);安徽省高校自然科学重大项目(KJ2015ZD42);皖南医学院弋矶山医院引进人才项目(YR201615)~~

摘　　要：目的:观察心肌肥厚时快激活延迟整流钾电流(rapidly activated delayed rectifier potassium channel,I_(Kr))和慢激活延迟整流钾电流(slowly activated delayed rectifier potassium channel,IKs)的变化,并探讨I_(Kr)和IKs阻断剂对心肌肥厚豚鼠室性心律失常发生的影响。方法:豚鼠分为假手术组和左心室肥厚(left ventricular hypertrophy,LVH)组,制备LVH模型。采用全细胞膜片钳技术记录心室肌细胞I_(Kr)和IKs电流,观察I_(Kr)和IKs电流的变化;给予豚鼠分别静脉注射I_(Kr)阻断剂多非利特(0.04 mg/kg)和IKs阻断剂chromanol 293B(0.1 mg/kg),观察其对LVH豚鼠QTc及室性心律失常发生的影响。结果:豚鼠胸主动脉缩窄6周后,与假手术组相比,室间隔厚度,左室后壁厚度,QTc间期和细胞电容显著增加(P<0.05或P<0.01);LVH心室肌细胞IKs明显减少[+60 m V:(0.36±0.03)p A/p F vs(0.58±0.05)p A/p F,P<0.01];LVH对I_(Kr)无明显影响。I_(Kr)阻断剂可显著延长LVH豚鼠QTc间期(P<0.01),并增加室性心律失常的发生。IKs阻断剂对LVH豚鼠QTc间期及室性心律失常的发生无明显影响。结论:IKs复极储备下调是心肌肥厚诱发室性心律失常的重要机制之一。Objective： To observe the changes of rapidly activated delayed rectifier potassium channel（IKr） and slowly activated delayed rectifier potassium channel（IKs） in cardiac hypertrophy and to evaluate the eff ects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy（LVH）. Methods： Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy（LVH） group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKrand IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers. Results： Compared with cardiac cells in the control group, the interventricular septal thickness at end systole（IVSs）, left ventricular posterior wall thickness at end systole（LVPWs）, QTc interval and cell capacitance in guinea pigs with LVH were significantly increased（P〈0.05）; while IKsdensities were significantly reduced [＋60 m V：（0.36±0.03） p A/p F vs（0.58±0.05） p A/p F, P〈0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval（P〈0.01） and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals. Conclusion： The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation of IKs.

关 键 词：心肌肥厚 快激活延迟整流钾电流 慢激活延迟整流钾电流 复极储备 室性心律失常 

分 类 号：R54[医药卫生—心血管疾病]