心脏收缩力调节对慢性心力衰竭兔心室肌电重构的影响

目的:观察心脏收缩力调节(cardiac contractility modulation, CCM)对慢性心力衰竭兔心室肌电重构的影响并探讨其可能的机制。方法:30只新西兰大白兔随机分为3组:假手术组、心衰组(采用升主动脉根部套扎法建立兔慢性心力衰竭模型)和心衰+CCM刺激组(模型制作成功后给予4周的CCM治疗)。电生理记录仪测定QTc和心室有效不应期(ventricular effective refrective period, VERP);采用RT-qPCR和Western blot检测心室肌Kv1.4、Kv4.3和缝隙连接蛋白43 (connexin 43, Cx43)的mRNA和蛋白的表达水平。结果:(1)实验第12周末,心衰兔QTc显著延长(P<0.05);实验第16周末,与心衰组相比,心衰+CCM组经4周CCM刺激后QTc显著缩短(P<0.05)。实验第16周末,与假手术组相比,心衰组、心衰+CCM组VERP显著延长(P<0.05);与心衰组相比,CCM可缩短心衰模型兔的VERP(P<0.05)。(2)与假手术组相比,心衰组心肌组织中Kv1.4、...

Effects of cardiac contractility modulation on ventricular electrical remodeling in rabbits with chronic heart failure

AIM: To investigate the effects of cardiac contractility modulation(CCM) on ventricular electrical remodeling in a rabbit model of chronic heart failure. METHODS: The rabbits were divided into sham group, heart failure(HF) group and HF+ CCM group. The rabbit model of chronic heart failure was established by ligating the ascending aortic root. Then electrical stimulations during the absolute refractory period were delivered lasting 6 h everyday for 4 weeks in rabbits of HF+ CCM group. The QTc and ventricular effective refrective period(VERP) were recorded. The protein and mRNA levels of Kv1.4, Kv4.3 and connexin 43(Cx43) were determined by Western blot and RT-qPCR. RESULTS: Compared with sham group, QTc were significantly prolonged in HF rabbits at week 12(P<0.05). CCM therapy shortened QTc of rabbits with heart failure at week 16(P<0.05). Compared with sham group, VERP significantly increased in HF group and HF+CCM group, while CCM therapy shortened VERP of rabbits with heart failure at week 16(P<0.05). Compared with sham group, the mRNA and protein levels of Kv1.4, Kv4.3 and Cx43 were decreased in HF group and HF+CCM group(P<0.05). However, CCM therapy restored the mRNA and protein levels of Kv1.4, Kv4.3 and Cx43 of rabbits with heart failure(P<0.05). CONCLUSION: CCM suppresses ventricular electrical remodeling in heart failure and the underlying mechanism may be associated with increasing Kv1.4, Kv4.3 and Cx43 expression.