双极射频消融治疗室壁瘤并发室性心律失常的机制探讨

Acute myocardial infarction can often lead to the formation of ventricular aneurysm, with electrically remodeling aneurysm adjacent tissue sustainable aggravating ventricular arrhythmia and endangering the patients' life.Reversing the ventricular electrical remodeling is important but difficult in cardiac surgical treatment. Bipolar radiofrequency ablation has advantages such as transmural, thoroughly, minimally injury and has been widely used in the treatment of atrial fibrillation. We practiced the application of this technology firstly in clinical treatment of ventricular arrhythmia related to ventricular aneurysm and achieved good therapeutic result, but its mechanism is still not clear. According to recent reports, gap junction, ion channel expression change could cause electrical remodeling. Our preliminary study also found the abnormal increases of differentially expressed proteins such as RyR2 and cytokines ICAM, CAMK relating to myocardial calcium metabolism were involved in the occurrence of ventricular arrhythmia related to ventricular aneurysm. So in this research " bipolar radiofrequency ablation reversing ventricular electrical remodeling " hypothesis is put forward, proposed by copying the ventricular aneurysm animal model induced by ventricular tachycardia, using electrophysiological techniques to map reentrant loop and target for bipolar transmural radiofrequency ablation during off-pump aneurysm repair with electrophysiological and ultrasound cardiography evaluation of curative effect. Observation of tissues surrounding ventricular aneurysm by pathological methods dynamically will be carried out, meanwhile observing the protein expression changes of RyR2, ICAM, CAMK and gap junction with RT-PCR and recording ion channel changes with patch clamp and verifying the research results clinically with protein detection to explore the mechanism of treatment in more depth, and provide a new strategy for the treatment of myocardial infarction related ventricular aneurysm in the future.

急性心肌梗死合并室壁瘤，瘤旁组织电重构加重室性心律失常危及生命,逆转心室电重构是心脏内外科治疗的重点和难点。双极射频消融具有透壁彻底、损伤小等优点而广泛用于房颤治疗。我们首次将该技术用于临床室壁瘤并发室性心律失常，取得良好疗效，但作用机制尚不清楚。新近报道，缝隙连接、离子通道表达改变是引起电重构的基础,我们前期研究发现，心肌细胞钙代谢相关的RyR2及细胞因子ICAM、CAMK等信号分子表达异常增高参与室壁瘤并发室性心律失常。故本课题提出："双极射频消融逆转室壁瘤电重构"假说，拟复制猪室壁瘤并发室性心动过速模型,用电生理技术标测折返环，针对行双极透壁射频消融，并联合冠脉搭桥及室壁瘤成形术；电生理及超声心动图评价疗效；观察瘤旁组织病理学改变及RyR2、ICAM、CAMK和缝隙连接等蛋白表达变化；分离瘤旁心肌细胞记录离子通道变化，临床行蛋白水平验证，深入探讨治疗机制，为急性心梗的治疗提供新策略。

急性心肌梗死合并室壁瘤，瘤旁组织电重构会加重室性心律失常危及生命,阻遏心室电重构是心脏内外科治疗的重点和难点。. 本课题建立急性心肌梗死后室壁瘤相关室性心动过速的实验猪模型，通过Carto三维电解剖标测系统准确定位导致室性心律失常折返环的解剖位置，然后根据“一字型”、“十字型”和“米字型”不同的全层心肌线性消融策略，探究双极射频消融术联合心肌再血管化和室壁瘤闭式成型对室壁瘤相关室性心动过速的遏制作用。消融前后分别获取正常心肌、室壁瘤核心区以及室壁瘤边缘区的心肌组织，利用组织病理学方法，进一步探究双极射频消融术阻遏瘤旁组织电重构的分子机制。.三维电解剖标测发现室壁瘤具有明显的电解剖边界，而且双极电压标准定义的低电压区面积（BV＜1.5mV）与病理学方法测得室壁瘤区域心内膜瘢痕面积之间具有良好的相关性（r=0.94, P＜0.05）。基质标测法发现致室性心律失常的基质（折返环）大都定位于室壁瘤边缘区（1.0mV＜BV＜1.5mV）。消融后即刻和8周后分别进行VT诱发，“米字型”消融VT的有效性分别达100%和83%，与“一字型”和“十字型”消融策略相比，“米字型”消融显著提高了VT的疗效（P＜0.05）。组织病理学结果表明：致室性心律失常基质所在的室壁瘤边缘区CX43、RyR2、ICAM、CAMK的表达较室壁瘤核心和正常心肌显著增高，而且CX43呈现去润盘化分布以及去磷酸化程度增加；然而消融后，组织出现均质性凝固性坏死，CX43、RyR2、ICAM、CAMK的表达显著下降。部分临床病例具有相似的组织病理学表现。双极射频消融实现了心内膜-心外膜同步、均质化基质改良的目的，通过显著降低CX43的表达，达到遏制室性心动过速的作用。. 本课题整合心脏内、外科先进治疗技术，一次性对室壁瘤相关室性心律失常实现了心肌缺血纠正，异常解剖矫治和电生理干预的多重治疗，为临床应用提供了理论依据，并且有助于整合医学模式的形成。