心房颤动转子的发生机制研究

Recently, the concept of rotors in human atrial fibrillation (AF) has been raising particularly enthusiasms in the clinical electrophysiological community since it is proven in patients with AF. However, mechanisms of formation, maintenance and modulation of rotors driving AF are currently unknown. This study will focus on the formation mechanisms of AF rotors. Incorporating spiral wave formation theory in physics and clincal characteristics of AF rotors, we propose a hypothesis that the formation of an AF rotor needs the following indispensables: one or two non-parallel wavefronts, a highly anisotropy atrial region and an extremely short atrial effective refractory period. First of all, we will conduct a computer simulation aiming to investigate the required formation conditions of AF rotors by using cross-field method, refractory period method and obstacle method. Secondly, rotors will be mapped on perfused atrial tissue model under stimulation of one or two non-parallel wavefronts separately. Finally, the electro-anatomical substrate of the formation of AF rotors and the approaches of minimizing the possibility of AF rotor formation will be investigated in dogs. With regard to implications of our proposal, we do consider the study we present will not only enrich our understandings on the theory of AF rotors, but also inspire some potentially new ablation strategies targeting the formation of AF rotors, and in turn, improve the long-term outcome of AF ablation.

晚近，心房颤动（房颤）的主导转子学说因被临床研究证实而颇受重视。然而，迄今有关房颤转子的形成、维持及调控等诸方面的机制均不清楚，本研究旨在探讨其形成机制。结合物理学上螺旋波形成的主要理论和房颤转子的主要临床特点，本研究提出如下假说：房颤转子的形成需要以下三个不可或缺的条件：⑴一个或两个传导方向成角的心房激动传导波阵面；⑵心房肌纤维排列高度各向异性区域；和⑶较短的局部心房肌不应期。主要研究内容包括：首先应用交叉场法、同向不应期法和障碍物法等螺旋波形成的主要方法对心房肌转子形成的可能机制进行计算机模拟；继之分别以单个和两个传导方向成角的快速心房传导波阵在离体灌注的心房肌组织上复制转子；最后探讨在体情况下转子形成的电解剖基础及具有减少转子形成作用的消融方法。本研究的实施不仅有助于进一步完善房颤转子学说的理论，而且有利于开发新的针对房颤转子形成机制的消融术式，从而使得房颤消融的效率获得进一步提高。

本研究选取了40只成年健康雄性比格犬（体重11-15Kg）， 首先通过外科手术方式植入起搏器，然后高频刺激心房1个月，制作犬慢性心房颤动模型，实时应用相应监测系统以及Powerlab软件系统进行信号分析，房颤模型成功率为95%。选取了完成房颤模型的比格犬，应用Ensite NavX系统进行特殊导管的高密度标测，并取病理做相应分析。结果显示，房颤转子的维持需要某些达到一定频率的特定驱动。当特定驱动终止时，房颤转子亦会终止，模式为突发突止。实验结果提示刺激-转子模式，高频刺激时可诱发房颤转子产生。通过对右心房进行电生理标测，发现了房颤持续时机制为转子的大折返环+转子轴心局部无序状态共存。病理证实转子轴心区域心肌细胞肥大，排列紊乱，细胞核畸形，肌束结构破坏，心肌纤维化成分增多，胶原容积积分显著增高 （27.75±2.99）% vs （17.95±3.20）%，P < 0.05。本研究通过动物实验对房颤转子理论进行了研究和论证，研究成果对于房颤触发及维持机制的研究具有重要的指导作用。