The effect of gene transfer with hepatocyte growth factor for pulmonary vascular hypoplasia in neonatal porcine model.
BACKGROUND
Severe degree of pulmonary vascular hypoplasia remains a major limitation in congenital heart surgery. Considering the potential effect of gene transfer with hepatocyte growth factor to induce the angiogenesis in the lung, we assessed the effects of hepatocyte growth factor gene transfer in neonatal porcine lung with pulmonary vascular hypoplasia to achieve treatment for severe pulmonary vascular hypoplasia.


METHODS
The model of pulmonary vascular hypoplasia was introduced with left pulmonary artery banding in piglet lung. After 7 days of pulmonary artery banding, piglets were transfected selectively to the left lung via the left pulmonary artery with a hemagglutinating virus of Japan E vector bearing the cDNA encoding human hepatocyte growth factor (H group) or control vector (C group).


RESULTS
Seven days after the transfection, selective angiography of the left pulmonary artery showed the progression of left pulmonary vascular hypoplasia of the left lung in the C group but a significant attenuation of left pulmonary vascular hypoplasia in the H group. A right pulmonary artery occlusion test showed a marked increase in right ventricular systolic pressure in the C group, but this was significantly attenuated in the H group (C: 22.0 +/- 2.9, H: 13.0 +/- 2.7 mm Hg; P < .05). Histologic examination revealed that hepatocyte growth factor gene transfection increased the pulmonary vasculature in the left lung.


CONCLUSIONS
Our results demonstrated that gene transfer of hepatocyte growth factor via the pulmonary artery showed the angiogenic effects in porcine model of pulmonary vascular hypoplasia after pulmonary artery banding.
Ono
Masamichi
M
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Sawa
Yoshiki
Y
Miyamoto
Yuji
Y
Fukushima
Norihide
N
Ichikawa
Hajime
H
Ishizaka
Toru
T
Kaneda
Yasufumi
Y
Matsuda
Hikaru
H
D000792:Angiography; D000818:Animals; D000831:Animals, Newborn; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011651:Pulmonary Artery / Q000002:abnormalities*; D029082:Sendai virus / Q000235:genetics; D013552:Swine; D014162:Transfection; D016278:Ventricular Function, Right / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology
D018076:DNA, Complementary; D017228:Hepatocyte Growth Factor