New method to improve the perfusion of a skeletal muscle in cardiomyoplasty -study of angiogenesis promoted by bFGF-.

组织血流量是影响骨骼肌功能的主要因素。背阔肌心肌成形术中，穿孔血管结扎导致移植物缺血，导致移植物疲劳，运动性能下降。血管延迟法改善了移植物心肌缺血，但需要4 ~ 8周的时间，不足以实现长期的心脏辅助。为了建立改善移植物灌注的新方法，我们研究了血管生成因子（bFGF和VEGF）对缺血组织的影响。心肌成形术中bFGF促进血管生成的实验：采用胶原热交联肝素化法研制bFGF缓释系统，移植于5只犬心肌和背阔肌之间。术后4周行肉眼及显微镜检查。在bFGF移植部位，结缔组织和血管内皮细胞增多。此外，还发现了许多毛细地层。结果表明，bFGF能促进缺血心肌血管生成，改善缺血心肌灌注。电穿刺辅助VEGF cdna编码质粒注射侧支循环发育：将裸vegf165编码质粒肌内注射Wistar/ST大鼠缺血后肢肌肉。立即，在一半的组中加入了选举[EP]。通过测量与对肢比较的血压比（BPR）和计算血管数量（血管造影评分）来评估疗效；]。基因转移后，BPR和AS均升高，且[IM+EP]组高于[IM]组。这些结果表明，通过电穿孔提高裸VEGF质粒DNA直接转染缺血组织IM基因的效率是可行的。

Tissue blood flow is the major factor of the function of skeletal muscle. In latissimus dorsi cardiomyoplasty, the ligation of perforation vessels causes skeletal muscle graft ischemia, and it contributes to the fatigue and lower performance of the muscle graft. Vascular delay methods improve the ischemia of muscle graft, but it needs 4 to 8 weeks long and not sufficient for long term cardiac assistance. To establish new method to improve the perfusion of the graft, we investigated an influence of angiogenic factors (bFGF and VEGF) on ischemic tissue.1. Experiment on the angiogenesis promoted by bFGF in cardiomyoplasty : We developed bFGF slow release system applying thermal crosslinking heparinization method of collagen, and transplanted it between myocardium and latissimus dorsi muscle in cardiomyoplasty of five dogs. Four weeks after operation, macroscopic and microscopic examination was performed. At the bFGF transplanted site, connective tissue and vascular endothelial cell were increased. Moreover, many capillary formations were seen. These results suggest that bFGF promote angiogenesis and improve the perfusion of ischemic muscle.2. Collateral circulation development by electroporation-assisted VEGF cDNA-encoding plasmid injection : A naked VEGF165-encoding plasmid was injected intramuscularly [IM] into the ischemic hind limb muscles of Wistar/ST rats. Immediately, electoporation [EP] was added in the half of the groups. The effect was assessed by measuring blood pressure ratio [BPR] comparing to the opposite limb, and counting the number of vessels [angiographic score ; AS]. After gene transfer, the BPR and AS increased, and was higher in [IM+EP] group than in [IM] group. These results suggest that the feasibility of enhancing the efficiency of direct IM gene transfer of naked VEGF plasmid DNA for ischemic tissue, by electroporation.