浦肯野系统参与心梗后室性心律失常的电生理机制研究: 基于超高密度三维标测技术

Purkinje fiber cells were less susceptible to ischemia than working cardiomyocytes. In vitro studies showed that purkinje cells surviving myocardial infarction presented arrhythmogenic properties. But post-infarction ventricular arrhythmias involving Purkinje system were comparatively uncommon. These preliminary studies provided evidence of abnormal conduction property of Purkinje system, the involvement of Purkinje system in the reentry of monomorphic ventricular tachycardia and their role in the initiation and maintenance of polymorphic ventricular tachycardia/ventricular fibrillation through the mechanism of triggered activity and abnormal automaticity. However, the specific mechanism was not well elucidated due to the lack of high-density mapping technique and the direct involvement of Purkinje system was not proven due to the absence of histopathological evidence. These researching gaps not only hampered our understanding of the electrophysiological mechanism of post-infarction ventricular arrhythmia, but also made an effective ablation strategy evasive. Thus, utilizing ultra high-density three dimensional mapping and histopatholocial study of endocardial purkinje system in a swine model of post-infarction ventricular arrhythmia, we sought to prove the following hypotheses: 1) after ischemic injury, Purkinje system experiences changes in electrophysiological properties and in the coupling pattern with the working myocardium, which may serve as arrhythmogenic substrate; 2) Triggered activity and/or abnormal automaticity of Purkinje system is the principle mechanism of post-infarction premature ventricular contraction-polymorphic ventricular tachycardia, while both Purkinje fiber in the peri-infarction zone and proximal purkinje system affected by ischemia can participate in the reentry of post-infarction monomorphic ventricular tachycardia; 3) ablation targeting the key component of Purkinje system related ventricular arrhythmia can effectively eliminate these ventricular arrhythmias.

研究发现心梗后浦肯野纤维细胞较容易存活，存在明显的致心律失常特性。但与浦肯野系统相关的心梗后室性心律失常报道较少。这些报道提供了初步证据支持心梗后浦肯野纤维系统存在传导异常、可构成单形性室速折返环成分、或通过触发和自律性增高机制参与多形性室速/室颤的启动和维持，但由于缺乏高密度标测手段，对机制的认识有明显的缺陷，且缺乏组织病理学直接证据。这阻碍了临床上针对性的导管消融治疗。我们拟在猪心梗后室性心律失常模型中通过超高密度三维标测及心内膜浦肯野系统组织病理染色，证明1）心梗后受缺血影响的浦肯野系统存在不同程度的电生理特性变化及与心室肌偶联的变化，即致心律失常基质；2）浦肯野纤维触发或自律性增高是心梗后室早-多形性室速发生的主要机制，而梗死灶边缘存活的浦肯野纤维及近端受缺血影响的浦肯野系统都可能参与心梗后单形性室速的折返；3）针对浦肯野系统参与的关键部位进行导管消融，能有效地治疗该类心律失常。

研究发现心梗后浦肯野纤维细胞较容易存活，存在明显的致心律失常特性。但与浦肯野系统相关的心梗后室性心律失常报道较少。这些报道提供了初步证据支持心梗后浦肯野纤维系统存在传导异常、可构成单形性室速折返环成分、或通过触发和自律性增高机制参与多形性室速/室颤的启动和维持，但由于缺乏高密度标测手段，对机制的认识有明显的缺陷，且缺乏组织病理学直接证据。我们的研究通过动物自身对照实验在犬心梗模型诱发室性心律失常，通过超高密度三维标测技术标测明确窦律下基质和室性心律失常机制，对病变心内膜浦肯野系统进行病理染色，对部分例数尝试导管消融。研究分为标测组和消融组，分别建模成功例数为9例和6例。超高密度标测均发现浦肯野系统向心室突破口发生变化，局部P电位出现振幅下降和电位异常，但局部V波基本保留。经电生理检查和超高密度标测发现两组可诱发浦肯野系统相关室性心律失常的例数分别为7例和3例，在消融组中对异常P电位进行点片状射频消融，可在术中达到室性心律失常不再诱发，即急性期成功。对9例标测组心梗后心内膜浦肯野系统进行卢戈氏液碘染色，均可见心梗中心区域（包括肉柱和假腱索部位）碘染色缺失。这些研究结果支持：1）心梗后浦肯野系统比普通工作心肌更容易受到缺血缺氧和/或再灌注损伤，且心梗后浦肯野系统与心室肌偶联发生变化；2）明确浦肯野系统病变可作为室性心律失常触发机制和单次折返机制的病灶，但未能证实梗死边缘区域的病变浦肯野纤维维持单形性室速折返环的普遍性；3）导管消融是治疗该类型室性心律失常的有效方式。