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

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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.