长期血浆内皮素-1水平升高对兔心室电生理特性及心律失常的影响

目的:探讨长期血浆内皮素-1(ET-1)水平升高对兔心室电生理特性及室性心律失常(VA)的影响。方法:雄性新西兰大耳兔30只,随机分为对照组(CTL组)和血浆ET-1升高组(ET-1组),每组15只。所有动物连续14d经耳缘静脉注射药物,其中ET-1组按10μg/(kg·d)剂量注射ET-1,而CTL组则给予注射0.9%生理盐水[1ml/(kg·d)]。所有动物完成药物注射7d后,在整体心脏Langendorff灌流条件下行离体电生理研究。同步记录起搏周长(PCL)为300ms时左室前游离壁心内膜(LAF-Endo)及心外膜(LAF-Epi)单相动作电位(MAP),并计算动作电位复极跨壁离散度(TDR);测量LAF-Epi的有效不应期(ERP),并构建标准动作电位恢复性质(AP-DR)曲线,计算标准APDR曲线最大斜率(Smax);于LAF-Epi行程控增频刺激,进行动作电位电交替(ALT)及室性心律失常(VA)诱发,记录诱发ALT及VA的最大PCL(PCLmax)。结果:与CTL组相比,ET-1组LAF-Epi及LAF-Endo的90%单相动作电位时程(MAPD90)、APDR曲线Smax、诱发ALT及VA的PCLmax中位数均增大(P均<0.05),而LAF-Epi的ERP/MAPD90(P<0.01)却明显减小;CTL组动物LAF-Epi的MAPD90短于LAF-Endo,而ET组动物LAF-Epi的MAPD90却较LAF-Endo延长(P均<0.05);TDR及LAF-Epi的ERP在两组间无明显差异(P均>0.05)。结论:长期血浆ET-1水平升高可引起心室正常复极顺序发生逆向改变、增大标准APDR曲线最大Smax及减小心室发生ALT的频率阈值,进而促进VA的发生。

Long-Term Elevated Plasma Endothelin-1 Damages the Electrophysiological Characteristics to Increase Ventricular Arrhythmia Susceptibility in the Langendorff-Perfused Rabbit Hearts

Objective:To determine the effects of long-term elevated plasma endothelin-1(ET-1) on the electrophysiological characteristics and arrhythmia of ventricle in the Langendorff-perfused rabbit hearts.Methods:Thirty male rabbits were equally divided into two groups randomly:control group(n=15,1 ml/kg normal saline injection per day for two weeks) and plasma ET-1 elevated group(n=15,ET-1 10 μg/kg per day for two weeks).The in vitro study was performed in a week after accomplishing the injection of drugs.To all the whole langendorff-perfused hearts,the monophasic action potential(MAP) of the endocardium(Endo) and epicardium(Epi),transmural dispersion of repolarization(TDR) and the effective refractory period(ERP) of Epi were recorded and measured in the anterior free wall(LAF) of left ventricle,respectively;the standard action potential duration restitution(APDR) curves were constructed;moreover,the programmed electrical stimulation was used to induce action potential duration alternans(ALT) and VA in the LAF.Results:Compared with the control group,the 90% of MAP duration(MAPD90) of Epi and Endo,the max slope(Smax) of APDR curves,the max pacing cycle length(PCL) medians of inducing the action potential duration ALT and VA were markedly increased(all P<0.05),but the ERP/MAPD90 of Epi was significantly decreased(P<0.01).In the control group,the MAPD90 of the Epi was shorter than that of Endo,while the MAPD90 of the Epi was longer in the ET-1 group(all P<0.05).There were no significant differences in TDR and ERP of Epi between the two groups(all P>0.05).Conclusion:The long-term elevated plasma ET-1 could reverse the sequence of repolarization between Endo and Epi,enhance the Smax of APDR curves and attenuate the threshold of action potential duration ALT,and all these facilitate the development of VA.