Myocardial angiogenesis treatment for ungraftable ischemic heart disease : Efficacy of intramural injection of human recombinant hepatocyte growth factor in conjunction with transmyocardial laser revascularization

经心肌激光血管重建术（TMLR）联合壁内注射血管生成因子可能通过血管生成等机制缓解不可移植缺血性心脏病患者的心绞痛状态。在本实验研究中，我们评估了TMLR和人重组肝细胞生长因子（human recombinant hepatocyte growth factor， IIHGF）内源性注射的疗效。[方法]对beagle进行近端LAD结扎。结扎LAD 1个月后，在每组（TMLR组、IIHGF组、TMLR+IIHGF组）行TMLR、IIHGF及TMLR+IIHGF联合治疗。在TMLR+IIHGF组中，先行TMLR，然后在TMLR通道周围的心肌中注射第二次HGF。每次治疗1个月后，分别用彩色微球法测定心肌血流（MBF）、超声显微镜法测定心肌血流（SS）、PCNA染色法测定新生血管形成情况，评价多巴酚丁胺应激或无多巴酚丁胺应激小鼠心肌血流（MBF）、局部心功能（SS）和组织化学分析。[结果]TMLR和IIHGF可改善LAD病变的MBF和SS。IIHGF组MBF和SS显著高于TMLR组。组织学上，与TMLR组相比，IIHGF组LAD病变中pcna阳性小动脉数量明显增加。IIHGF联合TMLR可提高TMLR对慢性缺血心肌MBF、SS和血管生成的影响。【结论】我们的数据表明，与TMLR相比，外壁注射HGF对慢性缺血心肌的血管生成和内在收缩状态有更明显的改善，并明显增强了TMLR的作用。

Transmyocardial laser revascularization (TMLR) and intramural injection of angiogenic factor has been proposed to alleviate angina status for patients with ungraftable ischemic heart disease by means of possible mechanism such as angiogenesis. In this experimental study, we evaluated the efficacy of TMLR and intramural injection of human recombinant hepatocyte growth factor (HGF) (IIHGF). [Methods] Beagles were subjected to proximl LAD ligation. After one month of LAD ligation, TMLR, IIHGF and combination of TMLR and IIHGF were performed in each beagle group (TMLR group, IIHGF group, TMLR+IIHGF group). In TMLR+IIHGF group, TMLR was first performed and second HGF were injected into the myocardium around the TMLR channels. One month after each treatment, regional myocardial blood flow (MBF), regional cardiac function (SS) with or without dobutamine stress, and histochemical analysis were evaluated using colored microsphere for MBF, sonomicrometer for SS, and PCNA staining for neovascularization. [Results] TMLR and IIHGF improved MBF and SS in the LAD lesion. MBF and SS in the IIHGF group was significantly higher than those in TMLR group. Histologically, in the LAD lesion, the number of PCNA-positive arterioles was markedly increased in the IIHGF group as compared with those of the TMLR group. IIHGF in conjunction with TMLR improved the effect of TMLR on the MBF, the SS and angiogenesis in chronic ischemic myocardium. [Conclusion] Our data demonstrated that intramural injection of HGF showed superior improvement of the angigenesis and the intrinsic contractile state as compared with TMLR in chronic ischemic myocardium and enhanced the effect of TMLR markedly.