消融Marshall韧带预防心肌梗死后猝死的实验研究

The malignant ventricular arrhythmias are the direct and major causes of sudden death in patients with myocardial infarction (MI). Sympathetic activation is an important factor for induction of malignant ventricular arrhythmias, and inhibition of effect of sympathetic activation on ventricles can prevent sudden death in those patients. Anatomical studies and our preliminary data found that the ligament of Marshall (LOM) is the crucial pathway by which left stellate ganglion innervates the ventricles, and LOM ablation eliminates the effects of stimulation of left stellate ganglion on ventricles. We have achieved preliminary success on the studies in which sudden death could be prevented by ablation of LOM in long QT symdrom. In this project, We propose for the first time that ablation of LOM may prevent malignant ventricular arrhythmias after MI. The animal models of acute MI and sudden death after will be constructed, and the relationship with sympathetic activity will be verified on these models. The effects of stimulation and ablation of LOM on ventricular electrophysiological properties in these models will be observed. The therapeutic results as well as the effects on atrium, sinoatrial node and atrioventricular node between ablation of ligament of Marshall and ablation of left stellate ganglion will be compared. This project will investigate the efficacy and safety of LOM ablation for prevention of malignant ventricular arrhythmias after MI, and may provide a new therapeutic strategy for prevention of sudden death after MI.

恶性室性心律失常是导致心梗患者猝死的直接和主要原因。交感神经激活是诱发心梗后恶性心律失常的重要因素，抑制交感神经对心室的影响可以预防心梗后猝死。解剖学及本实验室已有的研究结果提示：Marshall韧带是左侧星状神经节支配心室的重要通道，毁损Marshall韧带可消除左侧星状神经节刺激对心室的影响。前期消融Marshall韧带预防长QT综合征猝死已初步获得成功。本项目首次提出消融Marshall韧带预防心梗后恶性心律失常的新思路。本项目通过构建急性心梗和心梗猝死的大体动物模型，验证交感激活对其的影响；刺激或消融Marshall韧带，观察对心梗后心室电生理性质和室性心律失常的影响；比较Marshall韧带消融与左侧星状神经节消融对室性心律失常的预防效果以及对心房、窦房结、房室结的影响。本项目将探讨消融Marshall韧带预防心梗后恶性室性心律失常的有效性和安全性，为心梗后猝死的防治提供新的思路

本项目主要探索了Marshall韧带（ligament of Marshall，LOM）与心脏交感神经的解剖学及生理学联系，研究了消融LOM不同部位对犬心脏生理指标的影响，重点研究了消融LOM远段对房性及室性心律失常的影响。我们的解剖学研究发现，LOM与左侧星状神经节通过颈后神经节相连，是交感神经通向心脏的直接通路。组织学研究显示，LOM全程中均走行有大量交感神经纤维。心率变异性研究表明，消融LOM远段明显降低心脏交感神经支配强度，相对提高心脏副交感神经支配强度。电生理研究显示，消融LOM远段显著抑制左侧星状神经节功能，降低心脏交感神经支配活性，延长心房和心室有效不应期。在此基础上，建立六小时心房快速起搏模型、急性心肌梗死模型、心肌缺血再灌注模型，研究了消融LOM远段对心房急性电重构、心梗后急性期及心肌缺血再灌注室性心律失常的影响。结果表明，消融LOM远段有效抑制心房急性电重构，明显减少心梗后急性期及心肌缺血再灌注室性心律失常的发生。综上所述，本项目相关研究表明，LOM是交感神经支配心脏的重要通路，消融LOM远段能明显降低心脏交感神经支配强度，从而抑制交感神经相关的房性和室性心律失常。