冷冻球囊消融肺静脉对阵发性心房颤动心房肌电生理和基质变化影响的研究

Studies have showed that cryoballoon ablation of pulmonary veins was an effective and safe treatment for paroxysmal atrial fibrillation (AF), whose curative effect was not inferior to traditional radiofrequency ablation. However, it is not entirely clear that the effect of cryoballoon ablation of pulmonary veins on atrial electrical and substrate remodeling in patients with paroxysmal AF, which plays an important role in the initiation and pathogenesis of AF. Our preliminary results suggested that cryoballoon ablation of pulmonary veins could suppress the shortened atrial effective refractory period and increased atrial fibrosis produced by paroxysmal AF, which is an important part of atrial electrical and substrate remodeling. Therefore, we propose a hypothesis: 1.Cryoballoon ablation of pulmonary veins could suppress the atrial electrical and substrate remodeling induced by the paroxysmal AF, which is better than that of radiofrequency ablation; 2. The mechanism of cryoballoon ablation for AF therapy may be include both isolated pulmonary vein especially pulmonary veins vestibule and optimized atrial electrical and substrate remodeling. To test this hypothesis, animal model of paroxysmal AF is established and then the effect of AF ablation is compared between cryoballoon and radiofrequency ablation of pulmonary veins. Furthermore, it is evaluated that effect of cryoballoon and radiofrequency ablation on atrial electrophysiology, substrate and neural remodeling induced by paroxysmal AF, used in vivo electrophysiology, immunohistochemistry, ELISA, electron microscope, echocardiography, western blot and so on. The present study not only provide the experimental support in cryoballoon ablation for AF treatment, but also further reveal the mechanism of cryoballoon ablation for AF therapy in clinic.

研究提示肺静脉冷冻球囊消融是一种安全有效的治疗阵发性心房颤动（房颤）的新技术，其疗效非劣于传统的射频消融，但其对心房肌电生理和基质变化的影响知之甚少。我们预实验结果提示冷冻球囊消融可抑制AERP缩短和心房肌纤维化等重构，但其作用机制有待进一步探讨。为此我们提出假说：1.肺静脉冷冻消融与射频消融可抑制心房肌电生理和基质改变，且冷冻消融优于射频消融；2.冷冻消融治疗房颤的机制可能是：①通过隔离肺静脉尤其肺静脉前庭；②通过改变心房肌电生理和基质。为了验证这一假说，我们将通过建立房颤动物模型，采用在体电生理、免疫组化、ELISA、电镜技术、Western-blot等方法，明确冷冻消融与射频消融对心房肌电生理和基质变化的影响及其差异，探讨冷冻消融对阵发性房颤进展影响的机制。本研究从冷冻消融隔离肺静脉尤其前庭影响心房肌电生理和基质变化视点，揭示消融遏制房颤进展的机制，为临床提高治疗成功率提供实验支持。

研究提示肺静脉冷冻球囊消融是一种安全有效的治疗阵发性心房颤动（房颤）的新技术，其疗效非劣于传统的射频消融，但其对心房肌电生理和基质变化的影响知之甚少。本研究通过建立房颤动物模型，采用实验学方法，明确冷冻消融与射频消融对心房肌电生理和基质变化的影响及其差异，探讨冷冻消融对阵发性房颤进展影响的机制。将实验动物犬分四组，其中一组做假手术对照，一组心房间断起搏，一组心房间断起搏+肺静脉射频消融（射频消融组），一组心房间断起搏+肺静脉冷冻球囊消融（冷冻消融组）。犬饲养6月后，采用burst刺激诱发房颤，结果发现与心房起搏组相比，射频消融组和冷冻消融组房颤持续时间及次数均明显减少（P<0.05)；与射频消融组相比，冷冻消融组房颤持续时间明显减少（P<0.05)；表明冷冻消融较射频消融减小房颤诱发的疗效更优。电生理检测发现与心房起搏组相比，射频消融组和冷冻消融组AERP明显延长(P<0.05)，而AERP离散度、P波时限及其离散度显著减小(P<0.05)；与射频消融组相比，冷冻消融组的AERP显著延长(P<0.05)，而AERP离散度、P波时限及其离散度相对减小(P<0.05)；提示肺静脉冷冻消融可抑制阵发性房颤导致的电重构。彩超结果发现，与心房起搏组相比，射频消融组和冷冻消融组犬的LAD、LAVmin、LAVmax 和LVEDD均明显减小(P<0.05)；与射频消融组相比，冷冻消融组LAD、LAVmin和LAVmax均显著减少(P<0.05)；表明冷冻消融抑制房颤导致的结构重构。ELISA结果发现与心房起搏组相比，射频消融组和冷冻消融组犬TNF-α和IL-6水平明显降低（P<0.05）；与射频消融组相比，冷冻消融组可显著抑制右心房长期间断快速起搏引起的TNF-α和IL-6等的升高(P<0.05)。Western-blot结果发现与心房起搏组相比，射频消融组和冷冻消融组犬心房肌的MMP-9、TGF-β1和Smad2蛋白表达显著减少(P<0.05)，TIMP-1蛋白表达明显增加(P<0.05)；冷冻消融组较射频消融组MMP-9、TGF-β1和Smad2蛋白表达减少(P<0.05)，TIMP-1蛋白表达增加(P<0.05)。提示肺静脉冷冻消融可抑制阵发性房颤导致的炎症和纤维化等基质变化。该研究揭示冷冻消融遏制房颤进展的机制，为临床提高治疗成功率提供实验支持。