左心室心内膜起搏对犬失同步化心衰心室肌电生理特性的影响

About 30% of patients implanted with a single left ventricular (LV) lead positioned via the coronary sinus (CS) appear not to respond to cardiac resynchronization therapy (CRT).The LV pacing site is of critical importance for the CRT response but is often imposed by the CS anatomical constraints and may result in suboptimal resynchronization. Moreover, LV epicardial pacing may increase susceptibility to reentrant arrhythmias in some susceptible patients. Alternative pacing sites, such as endocardial LV pacing has been proposed to further improve CRT response rates and may potentially lower the risk of pacing-induced ventricular arrhythmia. However, the mechnaism is not fully understood. In the present study,the dyssynchronous canine heart failure model is establised by left bundle branch radiofrequency ablation and atrial tachypacing.LV electrical activation times, effective refractory period, QT interval and transmural dispersion of repolarization were then calculated to analyze the electrophysiologic properties of ventricular myocyte after resynchronization therapy. The induction of ventricular tachyarrhythmias is also studied. Isolated ventricular myocytes from the anterior and lateral mid myocardium were current and voltage clamped by the standard whole-cell patch-clamp technique for measurement of action potentials, transient outward K+ current (Ito), inward rectifier K+ current (IK1), delayed rectifier K+ currents (IK), and Ca2+ current (ICa). Immunohistochemical and Western blot analyses will be performed for the ion channels and the characterization of the expression of connexins Cx43. With the above ways,we want to test the hypothesis that LV endocardial pacing may partially reverse the electrical remodeling and the benefit of LV endocardial pacing is superior to that of epicaridal pacing.

心脏再同步化治疗（CRT）无反应率高达30%，左室起搏部位不佳是主要原因之一。传统左室起搏为冠状窦心外膜起搏，因冠状窦解剖限制，常植入非理想部位而降低CRT疗效且有致心律失常风险。研究发现左室心内膜起搏能进一步改善CRT疗效，但其对心室肌电生理特性影响及机制尚不清楚。本项目拟通过消融左束支及心房高频起搏建立犬失同步化心衰模型，观察左室心肌电学重构；应用EnSite三维标测技术，以心肌激动时间及顺序、不应期、QT间期、跨壁复极离散度等为观察指标，在体观察急性期和再同步化治疗后,左室心内、外膜起搏时心室电生理特性及室性心律失常诱发情况；采用膜片钳和分子生物学技术检测心内、外膜CRT治疗后左室心肌跨膜离子流变化及缝隙连接蛋白CX43表达，以论证左室心内膜起搏能够部分逆转心室电重构，作用优于心外膜起搏的假说，明确心内膜再同步化治疗逆转左室心肌区域性电重构的可能机制，为提高CRT反应率提供理论基础。

理论上左室心内膜起搏较冠状窦左室心外膜起搏心脏再同步治疗（CRT）更为生理，可能优于传统CRT治疗。本研究通过建立犬左束支阻滞心衰模型，对比左室心内膜起搏和心外膜起搏CRT治疗对于心衰犬心脏电生理特性影响及机制。研究结果如下：1）三维标测系统指导消融犬左束支较传统透视指导下消融左束支缩短手术时间和透视时间，增加成功率；（2）首次提出一种全新的在希氏束电极指导下犬房间隔穿刺方法；（3）通过心房高频起搏建立犬心衰模型，探索了一种新的左室心内膜起搏方法；（4）左室心内膜CRT治疗后QRS波有变窄趋势，左室心内膜起搏CRT治疗后心衰犬跨壁复极离散度（TDR）降低，可能会降低室性心律失常的发作；（5）证实心衰犬模型CACNG8、 KCNN3基因与LVEF存在相关性，心衰时出现KCNN3上调。心衰犬心肌细胞Navβ1 和 Navβ2对INaL通道呈现反向调节。