充血性心力衰竭兔心功能和电生理异常诱发室性心律失常及其机制

Effect and mechanism of ventricular arrhythmia induced by abnormality cardiac performance and electrophysiology in congestive heart failure rabbits

目的:探讨充血性心力衰竭(CHF)兔心功能和电生理异常诱发室性心律失常(VA)及其机制。方法:将雄性新西兰大耳白兔分为对照组(n=10)和CHF组(n=10)。经耳缘静脉注射异丙肾上腺素[0. 3 mg/(kg·d),连续注射3周]诱导,后继续喂养6个月制备CHF模型。采用超声心动图检测LVEDd、LVESd、LVEF、LVFS、Avmax、IVST、LVEDv和LVESv;心电图检测HR、PR间期、QT间期、ST段指标;记录单相动作电位(MAP),检测Maxdv/dt、APD10、APD20和APD90;程控刺激检测刺激周长(BCL)为150和200 ms时ERP150、ERP200、ERP150/APD90、ERP200/APD90和诱发VA的BCL及诱发率指标。酶解法分离单个心室肌细胞,全细胞膜片钳技术记录心室肌细胞L-型钙电流(ICa-L)及其电流-电压(I-V)相关性曲线。结果:与对照组比较,CHF组兔LVEDd和LVESd均明显延长,LVEF和LVFS均显著降低以及Avmax明显下降,IVST变薄以及LVEDv和LVESv均显著增大(P均<0. 05);CHF兔HR明显减慢,PR和QT间期均显著延长,ST段明显下移(P<0. 05);Maxdv/dt明显降低,APD10、APD20和APD90均显著延长。CHF兔ERP150和ERP200均显著延长,ERP150/APD90、ERP200/APD90均明显减小,被诱发VA的BCL显著延长和VA诱发率明显加大(P<0. 05);经电压钳制,CHF兔心室肌细胞ICa-L幅度明显增大,I-V相关性曲线显著下移,当指令电位为+10 mV时,CHF组兔心室肌细胞ICa-L电流密度明显大于对照组[(10. 02±0. 43)pA/pF vs(7. 21±0. 29)pA/pF,P<0. 01]。结论:CHF兔心脏功能明显减弱和电重构严重发生,产生非常明显利用VA发生的易感性,其机制可能与CHF心室肌细胞ICa-L显著增加,引起心室肌细胞内Ca2+超载和钙振荡相关。

Objective:To investigate effects and mechanism of ventricular arrhythmia(VA)induced by abnormality cardiac performance and electrophysiology with congestive heart failure(CHF)in rabbits.Methods:The male and healthy New Zealand rabbits were divide into control group and CHF group(n=10).The CHF models were successfully induced by injection isoproterenol(0.3 mg per kg per dayfor 3 weeks),after continuously breed for 6 months.The cardiac performance was evaluated through detecting LVEDd,LVESd,LVEF,LVFS,Avmax,IVST,LVEDv,and LVESv by echocardiography.Main cardioelectrophysiological parameters and values in the two groups were recorded such as HR,PR and QT interval,ST segment by recording ECG,Maxdv/dt,APD10,APD20 and APD90 from recording of monophasic action potential(MAP),and ERP150,ERP200,ERP150/APD90 and ERP200/APD90 with 150 ms and 200 ms of BCL,as well as BCL and inducibility rate of VA by Burst-pacing in left ventricular tissue of rabbits in vivo.The ICa-Land its I-V relationship curve were recorded via whole-cell patch clamp technique in enzymatically dissociated single rabbet ventricular myocytes in the two groups.Results:Compared with control group,the cardiac performance in rabbits in CHF group was severely attenuated with that LVEDd and LVESd were significantly lengthened,LVEF,LVFS,and Avmax were obviously decreased,IVST was thinned,while LVEDv and LVESv were notably enlarged(all P<0.05).The HR was significantly decreased,PR and QT interval were markedly lengthened,ST segment was descended down(all P<0.01).And Maxdv/dtwas markedly decreased,as well as APD10,APD20 and APD90 significantly prolongated in ventricular tissue of CHF rabbits in vivo.ERP150 and ERP200 were significantly lengthened,ERP150/APD90 and ERP200/APD90 were obviously decreased,as well as BCLs of occurrence of VA were notably prolongated,and induced rate of VA was significantly increased in ventricular tissue of CHF rabbits and control group(all P<0.05).With voltage clamp model,the current amplitude of ICa-Lmarkedly increased,and I-V relationship curve of ICa-Lwas severely altered down in different command potential in CHF ventricular myocytes as compared with that in control group.When holding potential was-60 mV,the current densities of ICa-Lin CHF group was significantly increased versus that in control group,as(10.02±0.43)pA/pF vs(7.21±0.29)pA/pF,P<0.01.Conclusion:It is indicated that the cardiac function is severely attenuated,electrical remodeling is significantly altered in CHF rabbit’s heart,and these changes contribute to increasing the susceptibility of VA induced by CHF.It is suggests that the the increasing of I+Ca-Linduces Ca2 overload and oscillations of CHF ventricular myocytes of rabbits.