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To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad5-HGF) transfer on post-infarct heart failure in a swine model.Twelve young Suzhong swine were randomly divided into 2 groups: the Ad5-HGF group (n=6) and the null-Ad5 group (n=6). Four weeks after left anterior descending coronary artery (LAD) ligation, Ad5-HGF was transferred into the myocardium via the right coronary artery. Coronary angiography and gated cardiac perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation, respectively, to evaluate collateral artery growth and cardiac perfusion. Then all animals were killed, the expression of HGF and α-smooth muscle actin (α-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry.Compared with the null-Ad5 group, higher expression of human HGF was observed in the myocardium in the Ad5-HGF group (109.3±7.8 vs 6.2±2.6, t=30.685, P<0.01). The left ventricular ejection fraction was higher in the Ad5-HGF group than in the null-Ad5group (43.9±4.3 vs 30.4±2.8, t=6.514, P< 0.01). From the 4th week to the 7th week after operation, left ventricular end systolic volume (42.1±3.0 vs 31.0±4.9, t=12.800, P<0.01) and left ventricular end diastolic volume (62.2±4.2 vs 55.0±4.8 t=13.207, P<0.01) were improved in the Ad5-HGF group. Cardiac perfusion was significantly improved in the Ad5-HGF group. In the Ad5-HGF group, growth of collateral arteries was obviously greater (average rank sum 9.17 vs 3.83, n=6, U=-2.687, P<0.01), and the number of α-SMA+vessels/mm2 was significantly greater (56.1±4.2 vs 16.4±3.5, t=17.731, P< 0.01) than in the null-Ad5group.High expression levels of human HGF were observed in the myocardium because of non-infarct-related vessel transfer. HGF can increase the number of functional arterioles and improve collateral artery growth. HGF can improve cardiac perfusion and heart function.