经皮球囊封堵冠状动脉法制备小型猪心肌梗死模型及评价

Establishment of miniature swine myocardial infarction model by percutaneous balloon occlusion method

目的:探讨球囊封堵法建立小型猪心肌梗死模型的可行性,以及骨髓间充质干细胞(MSCs)移植治疗心肌梗死疗效初探。方法:选用小型藏猪20只,麻醉后经股动脉置入经皮腔内冠状动脉成形术(percutaneoustransluminal coronary angioplasty,PTCA)球囊至左前降支中远段,完全堵闭血流90min,行心电图、心脏超声心动图、心肌核素显像、心脏核磁共振及病理检查。随机分2组:MSCs移植组,OTW球囊将MSCs移植到梗死心肌处;生理盐水组,注入等量生理盐水。观察2组的左室射血分数(LVEF)和短轴缩短率(FS)、左室舒张末期内径(EDV)和左室收缩末期内径(ESV)的变化。结果:20只猪均完成冠脉造影,造模成功10只,,死亡10只,成功率50%。与造模之前比,LVEF、FS显著下降(P<0.05),EDV、ESV显著延长。8周后,MSCs移植组均较移植前好转(P<0.05,P<0.01),而生理盐水组亦有所改善,但无显著差异;MSCs移植组的LVEF和FS较生理盐水组明显增加(P<0.05,P<0.01),MSCs移植组的EDV和ESV较生理盐水组明显缩少(P<0.05,P<0.01)。结论:球囊封堵法可成功建立小型猪心肌梗死模型,并且适合行骨髓干细胞移植的研究,但须特别注意预防心室纤颤的发生。MSCs移植可明显改善小型猪梗死心肌的功能。

AIM： To study the feasibility of establishing miniature swine myocardial infarction（ MI） model by percutaneous balloon occlusion method,and to investigate the effect of autologous mesenchymal stem cells（ MSCs） transplantation on treatment of acute MI. METHODS： Twenty Tibet miniatrue swine were included in the study and randomly divided into 2 groups. After anaesthesia,2. 5 mm × 15. 0 mm percutaneous transluminal coronary angioplasty balloon was positioned in the middle and distal-LAD by percutaneous femoral puncture in the right inguinal in the animals. The LAD flow was occluded for 90 min. The electrocardiogram（ ECG） ,echocardiography（ UCG） ,single photon emission computed tomography（ SPECT） ,magnetic resonance imaging（ MRI） and histopathology were examined. MSCs suspensions were injected to the infarct myocardium through infarct-related coronary artery by OTW balloon in MSCs transplantation group,while the control swine were injected with normal saline. Left ventricular ejection fraction（ LVEF） ,end diastolic volume（ EDV） , end systolic volume（ ESV） and fractional shortening（ FS） were observed. RESULTS： The coronary angiography was successfully performed in all 20 swine. Ten swine survived during the process of balloon occlusion,10 dead and the success rate reached 50% . After MI,LVEF and FS significantly decreased,while EDV and ESV significantly increased as compared to the values of pre-modeling（ P 0. 05） . Eight weeks after transplantation,the parameters observed above improved in MSCs group as compared to those of pre-transplantation（ P 0. 05,P 0. 01） . However,no significant difference of the parameters in saline group between pre-transplantation and after-transplantation was observed. Compared to saline group,LVEF and FS significantly increased in MSCs group（ P 0. 05,P 0. 01） with significant decreases in EDV and ESV（ P 0. 05,P 0. 01） . CONCLUSION： The miniature swine MI model is successfully established by percutaneous balloon occlusion method. Stem cells transplantation prevents the occurrence of ventricular fibrillation and obviously improves the myocardial functions.