EPCs促血管新生在心脏再同步化治疗改善心肌血流灌注中的作用及机制

Cardiac resynchronization therapy (CRT) improved chronic heart failure(CHF) prognosis, but the specific mechanism is still unknown. Electrical dyssynchrony increased ventricular stress in CHF, and decreased myocardial perfusion, therefore promoted myocardial remodeling. CRT reduced ventricular stress by synchronizing cardiac movement. Whether it will increase myocardial perfusion simultaneously? What is the mechanism? Our previous animal studied showed that dyssynchony CHF decreased stromal cell derived factor-1( SDF-1), which induced neovascularization reduction by endothelia progenitor cell(EPCs), and led to MVD reduction. Our pretest showed MVD increased after CRT in clinical patients. Previous studies showed EPCs were associated with CRT response. SDF-1 was secreted more under low stress, which may be induced by CRT. Thus, we supposed that CRT may increase SDF-1 concentration, and promote EPCs neovascularization. Then cardiac MVD will increase and improve myocardial perfusion. In order to prove it, the present study will perform clinical, canine and cell experiments. The results will be help in choosing optima patients for CRT, increasing CRT efficiency and improving CHF prognosis.

心脏再同步化治疗（CRT）逆转慢性心力衰竭（CHF）心室重构，但具体作用机制未阐明。CHF伴电失同步致心肌应力增加，血流灌注减少，加速心室重构。CRT同步心电活动降低室壁应力，那么CRT是否改善心肌血流灌注？机制是什么？我们前期动物研究发现心电失同步致室壁应力增高，SDF-1合成减少，不能诱导内皮祖细胞（EPCs）促血管新生，心脏微血管密度（MVD）减少致血流灌注不足。预实验示CRT增加左心MVD。EPCs与CRT疗相关；CRT降低室壁应力，而SDF-1在低机械应力时分泌增加。据此我们提出假设：CRT同步心室运动降低室壁应力，上调SDF-1介导的EPCs促血管新生，增加心脏MVD、改善血流灌注，逆转心室重构。据此，本项目拟结合临床、伴传导阻滞的心衰犬模型、细胞拉力刺激等方法，证明上述假说，从而为阐明CRT作用机制、提高CRT疗效、改善CHF预后提供科学依据。

心脏再同步化治疗（CRT）逆转慢性心力衰竭（CHF）心室重构，但具体作用机制未不清楚。本研究中通过临床研究观察CRT及新型起搏技术-左束支起搏术前及术后随访期间变化，发现接近生理的起搏技术可实现机械运动同步，改善左心室的有效功，减少无效做功，逆转心室重构，改善左心功能。而左心声学造影检查发现心脏微循环灌注损伤区域与机械运动异常室壁存在不一致性，且该区域晚期可恢复室壁运动，提示除了微循环灌注，神经内分泌、内皮细胞功能等都可能影响室壁运动。动物实验进一步证明双心室起搏纠正室壁运动失同步，并且可通过减少炎症因子、RAAS系统活化逆转左心室重构。综上证明CRT逆转心室结构并非简单的机械同步性，还通过影响心肌神经内分泌、炎症反应逆转左心室重构，该结果对于提高CRT疗效、改善心衰患者预后具有重要意义。