心导管介入冠状动脉封堵兔急性心肌梗死模型的建立

Establishment of a Rabbit Model of Acute Myocardial Infarction by Coronary Artery Catheterization

目的应用心导管介入方法封堵冠状动脉制备兔急性心肌梗死模型。方法选择雄性新西兰兔,先行冠状动脉造影,利用导引钢丝将微导管置于左前降支远端,将高分子栓塞剂与碘油混合配制成封闭胶,经微导管注入血管,造成急性心肌梗死。术前、术中和术后1周记录心电图变化。实验终点切取心肌组织标本分别行苏木素—伊红(H.E)染色、氯化硝基四氮唑蓝(NBT)染色、免疫组化染色。结果造模动物20只,存活16只。冠脉造影显示封闭胶持续滞留于左前降支远端,提示血管完全堵塞。心电图提示存在动态变化,ST段抬高,病理性Q波逐渐形成。心脏大体观测提示左心室前侧壁呈灰白色为梗死区。E染色提示梗死区局部纤维组织增生、疤痕形成、钙盐沉积,缺血区肌束变性、炎症细胞浸润,符合典型心肌梗死的病理变化。NBT染色后测定梗死面积为28.32%±5.21%。免疫组化染色提示缺血区CD34阳性面积和血管新生密度明显高于梗死区及正常组织区(P<0.05)。结论通过心导管介入方法制备兔急性心肌梗死模型成功,避免了开胸损伤对实验结果的影响,更符合临床急性心肌梗死的病理特点。

Objective To establish a rabbit model of acute myocardial infarction by coronary artery catheterization. Methods Twenty male New Zealand rabbits were used in this study. Coronary arteriography was performed at first and then a microcatheter was put into the distal segment of left anterior descending （LAD） coronary artery. The obstructive glue was prepared by mixing macromolecular embolic agent with iodized oil, and it was pushed into the vessel via the microzatheter to induce acute myocardial infarction. The changes of electrocardiogram were recorded after preoperative preparation, operation and 1 week later. Myocardium samples were prepared by hematoxylin-eosin （ HE）, nitroblue tetrazolium （ NBT）, and immunohistochemical staining at the end of experiment. Results 16 rabbits survived among the 20 operated animals. Coronary angiography displayed that the obstructive glue detained continuously in the distal segment of LAD inducing a complete occlusion. The dynamic ECG changes showed ST segment elevation and development of abnormal Q waves. The gross appearance of heart showed that the infarction area was at the antero-lateral wall of left ventricle and presented off-white color. HE staining showed fibrosis, scar formation and calcification in the infarction area, and myocardial degeneration and inflammatory cell infiltration in the ischemic area. All these were accorded with typical pathological changes of myocardial infarction. The infarction area was 28.32%±5.21%, determined by NBT staining. Immunohistochemical staining showed that the CD34 positive area and the density of neovasculature in the ischemic area were significantly higher than that in infarction or normal area （ P 〈 0.05）, Conclusion A rabbit model of acute myocardial infarction has been successfully established by an interventional procedure using coronary artery catheterization. It can avoid the adverse effects of open-chest operation, and the induced changes are more consistent with the pathological featuress of human acute myocardial infarction.