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Masamichi Ono
Yoshiki Sawa
Yuji Miyamoto
Norihide Fukushima
Hajime Ichikawa
Toru Ishizaka
Hikaru Matsuda
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Right arrow Congenital - cyanotic

J Thorac Cardiovasc Surg 2005;129:740-745
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

The effect of gene transfer with hepatocyte growth factor for pulmonary vascular hypoplasia in neonatal porcine model

Masamichi Ono, MD, PhDa, Yoshiki Sawa, MD, PhDa,*, Yuji Miyamoto, MD, PhDa, Norihide Fukushima, MD, PhDa, Hajime Ichikawa, MDa, Toru Ishizaka, MD, PhDa, Yasufumi Kaneda, MD, PhDb, Hikaru Matsuda, MD, PhDa

a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
b Division of Cardiovascular Surgery, Department of Gene Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan

Received for publication February 17, 2004; revisions received May 15, 2004; accepted for publication June 17, 2004.

* Address for reprints: Yoshiki Sawa, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. (E-mail: sawa{at}surg1.med.osaka-u.ac.jp).

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.






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