Brugada综合征心外膜转子在室性心律失常中电生理机制的研究

Recent studies have shown that epicardial ablation of right ventricular outflow tract in Brugada syndrome (BrS) can reduce and prevent arrhythmia. However, ablation strategy targeting abnormal potentials including fractionated electrogram and late potentials is still suboptimal. We found that in the mouse BrS model, polymorphic VT was caused by the initiation and perpetuation of the rotor in the right ventricular outflow tract. It has been demonstrated that the rotor is often formed in high repolarization dispersion or slow conduction area. Both of these areas are associated with the generation of abnormal potentials. This project is to further study in vitro canine wedge preparation of BrS model: 1) To study the role of fractionated electrogram / late potentials in rotor formation in ventricular tachycardia / ventricular fibrillation by simultaneous high-density endocardial and epicardial mapping combined with MAP recording. 2) Map and ablate the trajectory of singularity points of the rotor in order to uncover the key mechanism of maintenance of ventricular arrhythmia. 3) Demonstrate the dominant role of the epicardium in VT / VF maintenance by validating ineffectiveness of endocardial ablation. The results of the study will provide a theoretical basis for the future exploration of new ablation targets and ablation efficacy assessment.

最近研究证实，右室流出道心外膜消融可降低及预防Brugada综合征（BrS）所致心律失常事件。然而，以异常电位包括碎裂电位和晚电位为指导的消融策略结果仍不理想。我们发现小鼠BrS模型中，多形性室速可由右室流出道心外膜的转子（rotor）形成并维持 。一些研究发现，转子常在高复极离散度或慢传导区形成，这两个区域都与异常电位的产生相关。本项目拟在BrS犬体外楔形灌注模型中进一步研究：1）通过心内、外膜高密度标测结合正交电极验证，研究碎裂电位/晚电位在室速/室颤中的作用，识别参与转子形成的异常电位。2）标测心外膜室速/室颤中的转子奇点轨迹，指导消融，帮助阐述室性心律失常维持的关键机制。3）利用Lugol液行心内膜全层化学消融抑制心律失常无效，反证心外膜在室速/室颤维持中的主导作用。研究结果若能明确BrS心外膜转子在室性心律失常维持中的作用，将为今后探寻新消融靶点提供理论依据。

通过心房颤动病人颤动波的分析与训练，我们建立了以信息熵为基础的转子定位方法，通过对电图主频分析的结合，进一步优化了驱动转子的定位，并通过消融验证了方法并撰写了分析软件。在犬室速室颤模型中，我们通过心内膜及心外膜多电极同步标测的方法评价了Brugada综合征转子轨迹消融策略的可行性。发现消融可改变颤动的许多参数，但并不能直接终止室速室颤。由此我们认为在Brugada综合征的消融中，消融策略仍应以整片右室流出道心外膜为主。脉冲电场消融可能是Brugada综合征消融的更优解。项目共发表论文8篇，培养研究生5名。本项目的主要发现有助于对颤动驱动机制的探索和以此为基础的导管消融的发展。为今后房性及室性心律失常的防治策略提供实验依据和技术手段，具有一定的科学意义。