Liu Chao, Guo Peng-Ju, Li Sheng-Bo, Yao Xing-Xing, Jiao Zhou-Yang, Wen Bing, Xu Hua-Shan, Zhao Wen-Zeng
Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
J Huazhong Univ Sci Technolog Med Sci. 2014 Apr;34(2):220-224. doi: 10.1007/s11596-014-1262-8. Epub 2014 Apr 8.
The purpose of this study was to determine the combined effect of transmyocardial laser revascularization (TMLR) and the implantation of endothelial progenitor cells (EPCs) on cardiac function of ischemic hearts in canines. The left anterior descending artery (LAD) was occluded to establish the canine model of acute myocardial infarct (AMI). Four weeks later, the animals were randomly divided into four groups: TMLR group, in which transmyocardial laser-induced channels were established at the ischemic region; EPCs+TMLR group, in which EPCs were locally transplanted into laser-induced channels at the ischemic region; EPCs group, in which the EPCs were injected into the ischemic region; control group, in which the AMI animals received neither TMLR nor EPCs. The peripheral blood (50 mL) was sampled in all groups. Mononuclear cells from the peripheral blood were separated and cultured to obtain spindle-shaped attaching (AT) cells in vitro. AT cells were labeled with 1, 1'-dioctadecyl-1 to 3,3, 3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) before injecting into the laser-induced channels or ischemic region. Four weeks after the first operation, TMLR was performed in the TMLR group and EPCs+TMLR group, and at the same time, the EPCs originating from the AT cells were mixed with calcium alginate (CA). Then the EPCs-CA composites were implanted into myocardial channels induced by laser in the EPCs+TMLR group, and into the myocardial infarct area in the EPCs group. All dogs underwent echocardiography at second month after LAD occlusion. Finally the samples of myocardium around the LAD were subjected to histochemical and immunohistologic examinations. The results showed there was no significant difference in the diameter of left atrium and ventricle before treatment among all groups (P>0.05). Eight weeks after modeling, the regional contractility in the LAD territory in the EPCs+TMLR group was increased as compared with control group and TMLR group, but there was no significant difference between control group and TMLR group. Neoangiogenesis was observed in the EPCs+TMLR group, and the fibrosis was seen in the TMLR group. There was no significant difference in neoangiogenesis around the channels induced by laser among EPCs+TMLR, EPCs and TMLR groups. It was concluded that TMLR combined with EPCs could improve the regional and global cardiac function in AMI, and augment neovascularizaiton in channels of ischemic myocardium induced by laser.
本研究旨在确定经心肌激光血运重建术(TMLR)与内皮祖细胞(EPCs)植入对犬缺血性心脏心功能的联合作用。闭塞左冠状动脉前降支(LAD)以建立急性心肌梗死(AMI)犬模型。四周后,将动物随机分为四组:TMLR组,在缺血区域建立经心肌激光诱导通道;EPCs+TMLR组,将EPCs局部移植到缺血区域的激光诱导通道中;EPCs组,将EPCs注入缺血区域;对照组,AMI动物既未接受TMLR也未接受EPCs。所有组均采集外周血(50 mL)。分离并培养外周血中的单核细胞以在体外获得纺锤形贴壁(AT)细胞。在将AT细胞注入激光诱导通道或缺血区域之前,用1,1'-二油酰基-1,3,3,3',3'-四甲基吲哚羰花青高氯酸盐(DiI)标记。首次手术后四周,TMLR组和EPCs+TMLR组进行TMLR,同时,将源自AT细胞的EPCs与海藻酸钙(CA)混合。然后将EPCs-CA复合物植入EPCs+TMLR组的激光诱导心肌通道中,以及EPCs组的心肌梗死区域。所有犬在LAD闭塞后第二个月接受超声心动图检查。最后,对LAD周围的心肌样本进行组织化学和免疫组织学检查。结果显示,所有组治疗前左心房和心室直径无显著差异(P>0.05)。建模八周后,EPCs+TMLR组LAD区域的局部收缩力与对照组和TMLR组相比增加,但对照组和TMLR组之间无显著差异。EPCs+TMLR组观察到新生血管形成,TMLR组可见纤维化。EPCs+TMLR组、EPCs组和TMLR组激光诱导通道周围的新生血管形成无显著差异。结论是,TMLR联合EPCs可改善AMI的局部和整体心功能,并增强激光诱导的缺血心肌通道中的新生血管形成。