心脏再同步化治疗对缺血性心力衰竭犬的疗效及心肌钙通道电流的影响

The effects of cardiac resynchronization therapy on Ca^(2+) current in dyssynchronous ischemic heart failure

目的研究心脏再同步化治疗(CRT)对失同步化缺血性心力衰竭犬的疗效及钙离子通道电流(ICa)的影响。方法取西北犬行左束支射频消融术和冠状动脉前降支结扎术建立失同步化缺血性心力衰竭模型(n=14)。随机选取7只造模成功犬行CRT治疗,作为CRT组。另7只造模成功犬作为失同步化组。取5只正常犬作为对照组。CRT后6周(其它两组于相应时间点)检测心电图学、超声心动图及血流动力学指标,上述指标检测完毕后,分离左室侧壁和前壁心肌细胞,用全细胞膜片钳法检测ICa。结果与对照组相比较,失同步化组的RR间期缩短(420±55 ms vs 598±98 ms,P<0.05),QTc间期延长(433±46 ms vs 378±32 ms,P<0.05),QRS波时限延长(100±23 ms vs 53±8 ms,P<0.05),失同步化指数(DI)升高(80±22 ms vs 28±6 ms,P<0.05)。与失同步化组比较,CRT组QRS波时限缩短(73±11 ms vs 100±23 ms,P<0.05),降低了DI(32±24 ms vs 80±22 ms,P<0.05),缩短了QTc间期(392±36 ms vs 433±46 ms,P<0.05)。对照组左室前壁和侧壁的ICa密度峰值无差别(-4.7±0.3pA/pF vs-4.5±0.3 pA/pF,P>0.05)。失同步化组侧壁ICa电流密度低于前壁(-3.8±0.2 pA/pF vs-5.2±0.3 pA/pF,P<0.01)。CRT组侧壁和前壁的电流密度无差别(-4.5±0.2 pA/pF vs-4.5±0.3 pA/pF,P>0.05)。结论 CRT能部分地逆转失同步化缺血性心力衰竭的电重构与机械重构。

Objective To investigate the change in Ca^2± current （Ica ） in dessynchronous ischemic heart failure and the electrophysiological consequences of cardiac resynchronization therapy （CRT）. Methods The mode of dessynchronous ischemic heart failure of dogs was established by ablation of left bundle branch and ligation of left anterior descending artery （ n = 14）. They were divided into CRT group （ n = 7 ） and dessynchronous ischemic heart failure group （ n = 7 ）. After cardiac resynchronization therapy via pacing at light atrium, left ventricle and right ventricle for 6 weeks （n = 7 ）, the hemodynamic and echocardiographic parameters were measured, and then the dogs were killed, the myocytes of lateral and anterior left ventricular wall were dissected and the whole cell membranous clamp was used to detect the Ic,. The sham-operated group were used as control group（n=5）. Results Compared to control group, the RR intervals were shortened（420±55 msvs 598±98 ms, P〈0.05）, QTe prolonged（433±46 ms vs 378±32 ms, P〈0.05） , QRS prolonged（ 100±23 ms vs 53±8 ms, P〈0.05 ） , dyssynehrony index （DI） inereased （80±22 ms vs 28±6 ms,P〈0.05） in dyssynehronous ischemic heart failure group. CRT reduced the prolonged period of QRS（73±ll ms vs 100±23 ms , P〈0.05）, reduced DI（32±24 ms vs 80±22 ms, P〈0.05） and shortened QTc （392±36 ms vs 433 ±46 ms , P〈0.05 ） , when compared with dyssynchronous ischemic heart failure group. There was no significant difference in peak Ica density between lateral and anterior myocardium in control group（ -4.7±0. 3 pA/pF vs -4.5 ±0.3 pA/pF,P〉0.05 ）. There was a significant difference in peak ICa density between lateral and anterior myocardium in dyssynchronous ischemic heart failure group（ -3.8±0.2 pA/pF vs -5.2±0.3 pA/pF, P〈O. 01 ） , whereas no significant difference in peak Ica density was shown between lateral and anterior myocardium in CRT group（ -4.5±0.2 pA/pF vs -4.5±0.3 pA/pF, P〉O. 05 ）. Conclusions CRT can reverse partially the electrical and structural remodeling in dyssynchronous ischemic heart failure.