抑制晚钠电流对短QT间期心脏心电生理指标的影响及抗室性心律失常的机制  

Impact of late sodium current inhibition on cardiac electrophysiology parameters and ventricular arrhythmias in isolated Langendorff perfused rabbit hearts with short QT interval

作　　者：黄郁文 陈英 王程瑜 吴林[1] Huang Yuwen;Chen Ying;Wang Chengyu;Wu Lin(Department of Cardiology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院心血管内科,北京100034

出　　处：《中华心血管病杂志》2022年第11期1087-1093,共7页Chinese Journal of Cardiology

摘　　要：目的探讨抑制晚钠电流的药物对短QT间期心脏可能的电生理作用及其机制。方法采用Langendorff灌流装置制备兔离体心脏电生理研究模型。选择新西兰大耳白兔80只,首先任意选取34只,未用药时为对照A组(n=34)、给予IKATP开放剂吡那地尔后为吡那地尔A组(n=34),再从吡那地尔A组中选取27只,联用钠通道抑制剂或传统的用于治疗短QT综合征的药物奎尼丁后分为雷诺嗪联用组(n=9)、美西律联用组(n=9)、奎尼丁联用组(n=9)。在剩余的46只新西兰兔中选取19只,未用药时为对照B组(n=19),给予吡那地尔后为吡那地尔B组(n=19)。其余27只分为雷诺嗪单用组(n=9)、美西律单用组(n=9)、奎尼丁单用组(n=9)。采集对照A组、吡那地尔A组的心电生理参数,在对照B组、吡那地尔B组中采用程序电刺激诱发室性心律失常并采集心电图。采集吡那地尔联用组和单用药物组的心电生理参数,同时诱发室性心律失常并采集心电图。吡那地尔、雷诺嗪、美西律、奎尼丁药物浓度分别为30、10、30、1μmol/L。结果与对照A组相比,吡那地尔A组的QT间期、心外膜和心内膜动作电位复极化完成90%处的时程(MAPD_(90))缩短、跨室壁复极离散度(TDR)增大、有效不应期(ERP)和复极后不应期(PRR)降低(P<0.05)。与吡那地尔A组相比,美西律联用组、奎尼丁联用组心外膜和心内膜MAPD_(90)和QT间期延长(P<0.05),雷诺嗪联用组则不发生改变;TDR在3个联用组均显著降低,但ERP和PRR则延长(P<0.05)。程序电刺激时对照B组室性心律失常诱发率为0,吡那地尔B组升高至10/19(χ^(2)=13.6,P<0.05)。雷诺嗪联用组、美西律联用组和奎尼丁联用组室性心律失常的诱发率分别为1/9、1/9和0,均低于吡那地尔B组(χ^(2)=4.5、4.5、7.4,P均<0.05)。结论在QT间期缩短的心脏,抑制晚钠电流不会加重电生理异常,而且会降低恶性心律失常发生的危险性,其机制与逆转短QT情况下TDR的�Objective To determine the electrophysiological effects and related mechanisms of late sodium current inhibitors on hearts with short QT intervals.Methods The electrophysiological study was performed on isolated Langendorff perfused rabbit hearts.A total of 80 New Zealand White rabbits were used and 34 hearts without drug treatment were defined as control group A,these hearts were then treated with IKATP opener pinacidil,defined as pinacidil group A.Then,27 hearts from pinacidil group A were selected to receive combined perfusion with sodium channel inhibitors or quinidine,a traditional drug used to treat short QT syndrome,including ranolazine combined group(n=9),mexiletine combined group(n=9),and quinidine combined group(n=9).Nineteen out of the remaining 46 New Zealand rabbits were selected as control group B(no drug treatments,n=19),and then treated with pinacidil,defined as pinacidil group B(n=19).The remaining 27 rabbits were treated with sodium inhibitors or quinidine alone,including ranolazine alone group(n=9),mexiletine alone group(n=9),and quinidine alone group(n=9).Electrocardiogram(ECG)physiological parameters of control group A and pinacidil group A were collected.In control group B and pinacidil group B,programmed electrical stimulation was used to induce ventricular arrhythmias and ECG was collected.ECG physiological parameters and ventricular arrhythmia status of various groups were analyzed.The concentrations of pinacidil,ranolazine,mexiletine and quinidine used in this study were 30,10,30 and 1μmol/L,respectively.Results Compared with control group A,the QT interval,90%of the repolarization in epicardial and endocardial monophasic action potential duration(MAPD_(90)-Epi,MAPD_(90)-Endo)was shortened,the transmural dispersion of repolarization(TDR)was increased,and the effective refractor period(ERP)and post-repolarization refractoriness(PRR)were reduced in pinacidil group A(all P<0.05).Compared with the pinacidil group A,MAPD_(90)-Epi,MAPD_(90)-Endo,QT interval changes were reversed in quinidine

关 键 词：动作电位 晚钠电流抑制剂 跨室壁复极离散度 复极后不应期 心室颤动 

分 类 号：R541.7[医药卫生—心血管疾病]