中国小型猪冠状动脉慢性完全闭塞病变模型的建立

Establishment of the porcine model of chronic total occlusion by implantation of copper-stent in coronary artery

目的探讨采用铜丝缠绕型支架置入中国小型猪冠状动脉内的方法制作慢性完全闭塞病变(CTO)模型的可行性,建立一种新的CTO模型方法。方法 56头中国小型猪经股动脉穿刺,在前降支置入自制的铜丝缠绕型支架。分别在术前和术后1周、2周、4周、3个月、6个月时观察心电图、心脏超声和冠状动脉造影(CAG),然后处死取出心脏,取目标冠状动脉和梗死区域心肌,做病理学检查。结果 56头猪中共8头死亡,总的死亡率14.3%(8/56)。1周、2周时目标冠状动脉均为100%闭塞;4周、3月、6月时部分动物冠状动脉未完全闭塞(血栓机化再通),前向血流TIMI2～3级;完全闭塞的冠状动脉包括了绝对性闭塞(TIMI0级)和功能性闭塞(TIMI1级),并出现同侧的桥侧枝循环。以4周为CTO时间点,CTO模型的成功率为66.7%(28/42)。心肌病理学和心脏超声结果显示所有存活动物均发生了心肌梗死。冠状动脉病理学发现1、2周时闭塞病变处主要为血栓和炎症细胞浸润,4周、3个月、6个月时组血栓逐渐机化,发生纤维化,病变两端形成纤维帽,中间有微血管和孔道形成,与人体CTO病变极为相似。结论该CTO模型与人体CTO病变较为相似,而且有操作简单、创伤小、成本低、死亡率低、成功率高等诸多优点,可作为实验研究较好的动物模型。

Objective To create a new closed-chest model of chronic coronary total occlusion （CTO）by implanting copper-stent in coronary artery of China minipig.Methods Fifty six China minipigs were studied. Self-made copper-stents were implanted in the middle segment of the left anterior descending （LAD） after first diagonal branch coronary artery to induce total occlusion by thrombosis with standard catheterization techniques. Coronary angiography follow-up, troponin I, echocardiography, electrocardiogram and histologic evaluation were performed at 1 week in 7 pigs （group A）,2 weeks in 7 pigs （group B）, 4 weeks in 14 pigs（group C）, 3 months in 14 pigs（group D）,and 6 months in 14 pigs （group E） after the procedure, respectively.Results Eight of the total 56 pigs died while the rest 48 pigs survived in the end of the procedure. The survival rate was 85.7% and the mortality is about 14.3%.Follow-up angiography prior to sacrifice revealed total occlusion in 39 of 48 pigs （group A,n=5;group B,n=6;, group C,n=9; group D,n=9; groupE,n=10）,while nontotal occlusive lesions with an antegrade blood flow of TIMI grade 2 to 3 （because of recanalization） were detected only in group C（n=3）,group D （n=3）,and group E（n=3）.All the pigs in group A and group B（11 of 39） showed total occlusion （100% stenosis）. Bridging collateral flow was observed only in group C, group D, and group E. In this study, the chronic occlusion was defined as a duration of 4 weeks after copper-stents implantation. There were a total of 28 pigs with CTO in group C （9/12）,D （9/12）, and E （10/13）, and the rate of successful CTO model establishment is 66.7% （28/42）.Histology revealed fresh or organizing thrombus with persistent inflammation in the early group （group A and B）, and organized thrombus with fibrosis in the late groups （group C,D,E）. Interestingly, there were fibrotic components in the proximal and distal edges of the occlusions with softer, organizing thrombus in the middle of the CTO in the late group.Conclusions This study shows the feasibility and reproducibility of a new porcine coronary percutaneous CTO model. This model may be useful in improving our percutaneous treatment of CTO.