干预心脏自主神经治疗血管迷走性晕厥的新思路

Vasovagal syncope (VVS) is the most common cause of syncope in clinical practice, which can be subdivided into cardio-inhibitory, vasodepressor and mixed type. Till present there are no effective treatments for VVS. Bezold-Jarisch reflex is an important mechanism for VVS. As proved by experimental and clinical studies, ablation of multiple cardiac ganglionated plexi (GP) can inhibit the cardio-inhibitory element of Bezold-Jarisch reflex and can significantly relieve the symptoms of cardio-inhibitory VVS, while showing no effects for the other two types. The present study focuses on several novel ablation targets including ligament of Marshall (LOM) and certain critical GP. LOM is a key pathway involved in the onset of Bezold-Jarisch reflex and its ablation could inhibit this reflex from the very beginning, thus might be effective for all three types of VVS. The superior vena cava-aortic root (SVC-Ao) GP has been proved to be the “head station” of vagal fibers traveling to the sinus and AV nodes, while the right anterior GP (ARGP) and the right inferior GP (IRGP) function as the hubs for vagal innervations on sinus and AV nodes. Thus it’s feasible to treat cardio-inhibitory VVS just by the ablation of SVC-Ao GP or ARGP+IRGP, which is simpler and easier than the above-mentioned multiple GP ablation. The present study aims to investigate the effects and safety of LOM ablation, SVC-Ao GP ablation, and ARGP+IRGP ablation on VVS and the related mechanisms in a canine model, thus to find novel targets for autonomic interventions to treat VVS.

血管迷走性晕厥（VVS）是临床最常见的晕厥病因，可分为心脏抑制型、血管抑制型和混合型，目前尚无确切有效的治疗手段。Bezold-Jarisch反射是VVS的重要机制，消融心脏自主神经节丛（GP）可抑制该反射的心脏抑制环节，对心脏抑制型VVS疗效显著，但对其他类型无效。本课题提出了消融Marshall韧带（LOM）或关键GP的新思路：LOM与上述反射的起始密切相关，消融LOM可从起始环节抑制该反射，从而对三种类型VVS都可能有效。上腔静脉-主动脉根部（SVC-Ao）GP是迷走神经进入心脏的首站，其下游的右前和右下GP（ARGP和IRGP）是迷走神经支配窦房结和房室结的枢纽，仅消融SVC-Ao GP或ARGP+IRGP即可能对心脏抑制型VVS有效，且较已有的术式简单易行。本课题拟通过实验犬VVS模型，探讨上述新的消融术式对VVS的疗效、作用机制及安全性，寻找自主神经干预治疗VVS的最佳靶点。

本课题采用犬Bezold-Jarisch反射模型模拟血管迷走性晕厥，对血管迷走性晕厥的自主神经机制进行了研究。在血管迷走性晕厥模型中观察到两种不同类型的自主神经反应，并发现特征性的交感神经放电可能对血管迷走性晕厥有保护作用。同时通过心率变异性分析，研究了临床血管迷走性晕厥患者和对照在倾斜试验过程中的自主神经活性变化，发现血管迷走性晕厥患者存在自主神经活动的异常。在此基础上，研究了Marshall韧带消融和选择性右前神经节丛（anterior right ganglionated plexus，ARGP）+右下神经节丛（inferior right ganglionated plexus，IRGP）消融对犬血管迷走性晕厥模型的治疗作用。结果表明Marshall韧带消融并不能显著抑制血管迷走性晕厥模型中的心率和血压下降。而选择性ARGP+IRGP消融可显著抑制血管迷走性晕厥模型中的心率下降反应，但不能显著抑制血压下降反应。上述结果为选择性ARGP+IRGP消融治疗心脏抑制型血管迷走性晕厥提供了实验依据。