右房游离壁切口致心律失常作用的动物实验研究

The incision of the right atrial free wall （RAFW） is a routine access to the surgical treatment of congenital heart disease or acquired heart disease. Incisional scar related atrial tachycardia (AT) is a common complication after surgery. Previous studies demonstrated that most of these ATs were macro-reentrant tachycardias and their slow conduction area often located in the critical isthmus between the surgical scars and the tricuspid annulus (TA). However, the arrhythmogenecity of such incision and whether it is preventable remains unknown. The aim of this study is to make animal models recapitulating the different conventional surgical incisions and the modified incision and thus to test the electric property and the histological changes of the isthmus between incisional line and the TA. The low voltage area of RAFW, conduction velocity and the local refractory period of the isthmus will be also checked based on 3-D mapping. After these electrical tests, programmed electrical stimulation will be delivered to induce AT. Detailed 3-D activation map of the RA will be created by obtaining contact bipolar electrograms (150-200 points) during AT, the reentrant circuit and the key isthmus will also be analyzed. The histological changes of the surrounding tissue will be examined by HE staining, Masson staining and electron microscopy. The arrhythmogenecity of the surgical incisional line on the RAFW will be demonstrated and the feasibility of the preventable incisional line will be verified in the study.The study results might provide the theoretical basis to prevent post procedural ATs of surgical incisions on the RAFW.

经右房游离壁切口是治疗先天性心脏病或获得性心脏病的常规术式，术后部分患者易并发快速性房性心动过速（房速）。临床研究发现该心律失常的发生多与切口直接或间接相关，但很难解释为何此类心律失常仅发生于约5-10％的术后患者而非所有患者。发生该心律失常的病理基础相对明确，但其致心律失常的电学基础了解甚少，相应预防策略的研究更是罕见。本研究根据切口与三尖瓣环的距离，模拟不同的右房游离壁外科切口及新型改良切口制备动物模型。在窦律和起搏下，利用三维电解剖标测技术确定右房游离壁的低电压区，明确切口与三尖瓣环的相对位置并测量切口与三尖瓣环之间组织的传导速度及有效不应期。分别从高位右房及冠状窦口进行程序电刺激，观察房速诱发比例和诱发房速的周长，并在房速状态下构建右房三维电解剖激动模型，分析缓慢传导区的位置以及折返径路。应用HE染色、Masson染色和电镜检查等手段分析右心房游离壁不同切口周边组织的组织学改变。

经右房游离壁切口治疗先天性心脏病及获得性心脏病后，最常见的并发症是房性心动过速。房速发作时，不仅出现心悸、乏力、呼吸困难等症状，还可因房速持续发作伴快速心室率，恶化或加重心功能不全。此外，房速发作伴1:1房室传导，可导致急性血流动力学紊乱，患者可出现先兆晕厥、晕厥或猝死。研究发现，药物治疗常常不能有效控制此类房速的心室率。因此，迫切需要系统地研究这种心律失常的发生机制，从源头上预防或减少这种心律失常的发生。我们研究了右房游离壁外科切口致心律失常作用的电生理及组织学基础，并验证改良的右房切口（将切口扩展至三尖瓣环和下腔静脉）是否可以预防外科术后大折返性房性心动过速的发生。所有30头试验猪造模后饲养8周，再次全麻下开胸，穿刺股静脉后通过标测电极导管于右心耳内行程序刺激诱发房性心律失常，记录其电生理学参数。如可诱发持续性外科术后大折返性房性心动过速，则于三维电解剖标测系统导航下行心动过速的激动标测及拖带标测。并于不同起搏周长下测试各模型通道的传导特性。记录切口相关心房组织的组织学特征。 结果 宽通道组及窄通道组均有试验猪可被诱发持续性外科术后大折返性房性心动过速并完成标测（A组1/6，16.7%；B组5/12，41.7%），但封闭通道组及假手术组试验猪均未能诱发心律失常（P=0.087）。以20ms跨度行周长递减的心房起搏（350~270ms），各组跨越20mm长手术切口至三尖瓣环间通道的传导时间分别为：B组5mm通道为29.2±2.2ms，10mm通道为31.0±4.2ms，A组15mm通道为26.0±1.9ms，D组假手术组为17.0±1.4ms（P=0.017）。与传导特性相关的组织学结果可见，手术切口与三尖瓣环或下腔静脉间的通道越宽，其中的心房肌组织越健康。在C组（改良切口）中，两侧通道均被致密疤痕所替代并造成完全传导阻滞。手术切口与三尖瓣环或下腔静脉间的通道具有致心律失常作用，通道的宽度决定了其传导特性。结果证实改良的右房切口（将右房游离壁切口延伸至TA及IVC）可预防外科术后大折返性房性心动过速的发生。