左心室心内、外膜起搏CRT改善失同步化心力衰竭左心室收缩功能的效果与机制

Cardiac resynchronization therapy (CRT) can significantly restore left ventricular systolic function by improving the electrical synchronicity, which has demonstrated to be main effective therapy for the dyssynchronous heart failure (DHF). However, left ventricular epicardial pacing CRT shows different effect compared to endocardial pacing. To explore the mechanism of different effect between epicardial pacing and endocardial pacing CRT, we performed series of works in preliminary stage, and found CRT may directly improve myocardial systolic function. Therefore, we presume the main reason for different left ventricle systolic function improvement in DHF between epicardial pacing and endocardial pacing CRT lies in here, that CRT On one hand improve the electrical synchronicity, on the other hand it directly improve the myocardial contractility, ultimately improve the whole left ventricular systolic function. Different improvements in electrical synchronicity and different influences on calcium recycling proteins among left ventricle subendocardial, middle, and subepicardial muscle layer, account for the main reasons for this different effect on LV systolic function between epicardial pacing and endocardial pacing CRT. According to the above hypothesis, first of all, we compares the improvement of left ventricle systolic function in DHF of endocardial pacing CRT with that of epicardial pacing. Furthermore, we explore the the effect and molecular mechanism of improvement in cardiac electrical synchronicity and left ventricular myocardial systolic function, respectively. This research not only clarify the mechanism of CRT, but also provide the theoretical and experimental basis for the improvement in clinical CRT implementation.

心脏再同步化治疗(CRT)是目前国内外治疗失同步化心衰(DHF)的主要治疗手段之一，能够显著改善左心室收缩功能，但左心室心外膜起搏和心内膜起搏CRT的治疗效果不同。为明确两种CRT效果不同的机制，我们进行了系列前期工作，发现CRT也可不依赖于改善电同步性而直接改善心肌收缩功能，建立工作假说如下：CRT一方面通过改善电同步性，另一方面通过直接增强心肌收缩功能，最终改善左心室收缩功能。心外膜和心内膜起搏CRT改善心衰时心脏电同步性的不同以及改善心室肌三层心肌细胞与钙循环相关的蛋白功能的不同，是两种CRT治疗效果不同的主要原因。本项目首先进行左心室心外膜起搏和心内膜起搏CRT改善DHF左心室收缩功能的效果的比较研究；进一步研究两者改善心脏电同步性以及左心室心肌收缩功能的效果与分子机制。研究结果不仅为阐明CRT的作用机制提供了新思路，而且为临床进一步改进CRT治疗方法提供了理论与实验依据。

心脏再同步化治疗(CRT) 能够显著改善左心室收缩功能，是目前国内外治疗失同步化心衰(DHF)的主要手段之一，但目前有1/3 DHF患者对常规心外膜起搏CRT无反应。有学者认为，心内膜起搏CRT在改善心功能方面可能优于心外膜起搏CRT，但其作用效果和机制尚不明确。本项目通过建立犬失同步心衰心内膜起搏CRT和心外膜起搏CRT模型，结合超声心动图新技术及分子生物学等方法，对左心室心外膜起搏和心内膜起搏CRT改善DHF左心功能的效果进行比较及机制探讨。课题完成顺利，研究结果明确了CRT可以改善心脏电同步性及左心室收缩和舒张功能，且心内膜起搏CRT优于心外膜起搏CRT。其主要机制是CRT可增加心肌细胞钙离子循环相关蛋白SERCA2a mRNA及蛋白表达。且与心外膜起搏CRT相比，心内膜起搏CRT的SERCA2a表达增高更为显著。因此，我们得到结论，心内膜起搏CRT可更好地增强心肌收缩力及改善失同步心衰左室电同步性，从而最终改善左室收缩和舒张功能。研究结果不仅为阐明CRT的作用机制提供了新思路，而且为临床进一步改进CRT治疗方法提供了实验与理论依据。研究结果已发表论文11篇，其中SCI收录论文7篇（总IF值19.508）。