心脏自主神经重塑在房颤射频消融术后房颤复发中的作用机制研究

Atrial fibrillation (AF) is one of the commonest arrhythmias in clinical. At present radiofrequency ablation has become an important treatment strategy for AF, but the recurrence rate after radiofrequency ablation is still high. It has been shown that cardiac autonomic nerve played an important role in trigger and maintenance of AF, but it is unclear whether there is cardiac neural remodeling and nerve regeneration after AF ablation. And the relation between cardiac nerve regeneration and the recurrence of AF after radiofrequency ablation has also not been described in previous studies. Studies has shown that cardiac nerve had the ability of regeneration and remodeling in some diseases, and which might lead to the change of cardiac electrophysiology and myocardial contraction. In our former study we found that the sympathetic nerve have the ability of regeneration after AF ablation. In this study, we plan to observe cardiac neural remodeling and inducibility of AF after pulmonary vein isolation and ganglioned plexus ablation in canine model of AF. Then the possible mechanisms of cardiac neural remodeling and AF evoked by neural remodeling will be investigated with histological and molecular biological method. The study will help us to understand the mechanism of AF recurrence after AF ablation from the aspect of cardac neural remodeling, and it will provide some new ideas for the prevention of atrial fibrillation recurrence after AF ablation.

射频消融目前已成为心房颤动（房颤）治疗的重要手段，但消融术后房颤的复发率仍然较高。心脏自主神经与房颤的触发与维持有密切关系，是否心脏射频消融术后存在心脏自主神经再生和重塑，以及其与房颤复发的关系尚不明确。既往文献报道心脏自主神经具有再生和重塑能力，并能引起心脏电生理及心肌收缩功能的变化。前期预实验也我们发现自主神经节消融术后存在心脏自主神经再生和重塑，因此，本研究拟在犬房颤模型上，考察射频消融术后心脏自主神经再生和重塑情况，以及房颤可诱导性的变化，并从组织学和分子生物学水平探讨神经重塑的机制以及神经重塑引起房颤复发的机制。本研究的实施将有助于我们从神经再生的角度理解射频消融术后房颤的复发，为防治消融术后房颤复发提供新的思路。

射频消融是心房颤动重要的治疗手段，但消融术后房颤的复发率仍然较高。心脏自主神经与房颤的触发与维持有密切关系，心脏射频消融术后是否存在心脏自主神经再生和重塑，以及其与房颤复发的关系尚不明确。. 本研究在犬自主神经节射频消融模型上，观察了射频消融术后心脏自主神经再生和重塑的情况以及房颤可诱导性的变化，并从组织学和分子生物学水平探讨了自主神经重塑的机制，初步探讨了心脏自主神经重塑与房颤复发的关系。. 研究结果提示心脏自主神经节消融术后4周消融周边区域有明显的交感神经纤维再生，而副交感神经纤维无明显再生。电生理检查提示自主神经节消融后即刻心房有效不应期低于正常水平，但随着时间推移心房有效不应期逐渐恢复至正常，房颤可诱导性逐渐恢复接近消融前水平。分子生物学检测结果提示消融术后与交感神经再生相关的神经生长因子、生长相关蛋白-43及酪氨酸羟化酶水平明显升高，而与副交感神经再生相关的神经营养因子Neurturin的水平无明显增加。心脏自主神经节消融后，给予外源性神经生长因子能够明显促进交感神经的再生，明显增加房颤的可诱导性。. 该研究结果的发现有助于从神经的角度理解消融术后房颤复发的机制，为预防消融术后房颤复发提供新的思路。