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

心肌血管生成治疗不可移植缺血性心脏病：壁内注射人重组肝细胞生长因子联合经心肌激光血运重建的疗效

• 批准号: 10671255
• 负责人: TAKAHASHI Toshiki
• 金额: $ 2.3万
• 依托单位: YAMAGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671255/
• 关键词: transmyocardial laser revascularization; angiogenic factor; hepatocyte growth factor; ischemic heart disease; chronic ischemic myocardium; regional myocardial blood flow; cardiac function; レーサー心筋内血管新生術; 慣性心筋虚血

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.

激光心肌血运重建术(TMLR)和血管生成因子的壁内注射是通过血管生成等可能的机制来缓解不能移植的缺血性心脏病患者的心绞痛状态。在这项实验研究中，我们评价了TMLR和壁内注射人重组肝细胞生长因子(IIHGF)的疗效。[方法]采用近侧左前降支结扎动物模型。LAD结扎1个月后，每组(TMLR组、IIHGF组、TMLR+IIHGF组)分别行TMLR、IIHGF及TMLR+IIHGF联合治疗。TMLR+IIHGF组首先行TMLR，然后在TMLR通道周围心肌内注射HGF。治疗1个月后，用彩色微球检测心肌血流量(MBF)、心肌局部心功能(SS)及组织化学方法检测心肌血流量(SS)，用声学显微镜检测SS，用增殖细胞核抗原染色检测新生血管。[结果]TMLR和IIHGF可改善LAD病变的MBF和SS。IIHGF组的MBF和SS显著高于TMLR组。组织学上，与TMLR组相比，IIHGF组在LAD损伤处的增殖细胞核抗原阳性小动脉数目明显增多。IIHGF联合TMLR可改善TMLR对慢性缺血心肌MBF、SS和血管生成的影响。[结论]与TMLR相比，壁内注射HGF对慢性缺血心肌的血管形成和固有收缩状态有明显的改善作用，并显著增强TMLR的作用。

项目成果

Yanaguchi,et al: "Superior angiogenic effect of hepatocyte growth factor through intramyocardial injection as compared with transmyocardial laser revascularization in chronic ischemic myocardium"Circulation. 99bupp(Z). J-598 (1999)

Yanaguchi 等人：“在慢性缺血性心肌中，与经心肌激光血运重建相比，通过心肌内注射肝细胞生长因子具有优越的血管生成作用”循环。

Yamaguchi T,Sawa Y,Nishimura M,et al.: "Superior angiogenic effect of hepatocyte growth factor through intramyocardial injection as compared with transmyocardial laser revascularization in chronic ischemic myocardium"Circulation 99(suppl I). I-598. (1999)

Yamaguchi T、Sawa Y、Nishimura M 等人：“与慢性缺血性心肌中的跨心肌激光血运重建相比，通过心肌内注射肝细胞生长因子的血管生成效果更佳”Circulation 99（补充材料 I）。

Yamaguchi T,Matsuda H,Takahashi T,et al.: "Hepatocyte grow factor enhances the effect of transmyocardial laser revascularization in the ischemic myocardium"Circulation 98(suppl I). I-121. (1998)

Yamaguchi T,Matsuda H,Takahashi T,et al.：“肝细胞生长因子增强了缺血心肌中跨心肌激光血运重建的效果”Circulation 98(suppl I)。

Yamaguchi T, Matsuda H, Takahashi T, et al.: "Hepatocyte growth factor enhances the effect of transmyocardial laser revascularization in the ischemic myocardium."Circulation 98 (suppl I). I-121. (1998)

Yamaguchi T、Matsuda H、Takahashi T 等人：“肝细胞生长因子增强了缺血心肌中跨心肌激光血运重建的效果。”Circulation 98（补充材料 I）。

Yamaguchi T, Sawa Y, Nishimura M, et al.: "Superior angiogenic effect of hepatocyte growth factor through intramyocardial injections as compared with transmyocardial laser revasculariztion in chronic ischemic myocardium."Circulation 99 (suppl I). I-598. (

Yamaguchi T、Sawa Y、Nishimura M 等人：“与慢性缺血性心肌中的经心肌激光血运重建相比，通过心肌内注射肝细胞生长因子的血管生成效果更佳。”Circulation 99（补充材料 I）。