Published ahead of print on March 11, 2005, doi:10.1164/rccm.200411-1518OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200411-1518OC
Induction of Compensatory Lung Growth in Pulmonary Emphysema Improves Surgical Outcomes in RatsDepartment of Surgery, Division of Molecular Regenerative Medicine, Course of Advanced Medicine, and Department of Gene Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan Correspondence and requests for reprints should be addressed to Hikaru Matsuda, M.D., Ph.D., Department of Surgery, Osaka University Graduate School of Medicine, E1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: n-shige{at}blue.ocn.ne.jp Rationale and Objectives: Although lung volume reduction surgery (LVRS) has been widely used as a therapeutic strategy for pulmonary emphysema, the procedure carries significant disadvantages, including significant operative mortality and a limited duration of effective response. Pulmonary resection is known to elicit compensatory growth in remnant lung tissues; however, it remains unclear whether and how compensatory growth occurs and contributes to clinical outcomes after LVRS. The goal of the present study was to characterize the role of hepatocyte growth factor (HGF) in compensatory lung growth after LVRS in a rat model of elastase-induced emphysema, since HGF is a potent pulmotrophic factor responsible for the regeneration of lung parenchyma in damaged lungs, including after a pulmonary resection. Methods and Main Results: Unexpectedly, LVRS did not cause apparent increases in the endogenous HGF profiles of emphysematous lungs. Further, the lowered HGF production reflected a histologically inferior regenerative capacity in remnant lungs and was linked with impaired pulmonary functional recoveries after LVRS. When HGF was exogenously supplemented by gene transfection into emphysematous lungs simultaneously with LVRS, compensatory lung growth (as evidenced by increased lobe weight and alveolar regeneration and angiogenesis) was significantly enhanced as compared with rats that underwent LVRS alone. Consequently, pulmonary function and gas exchange were also significantly improved. Conclusions: We concluded that the induction of compensatory growth by growth factors after LVRS may be a new strategy to further improve clinical outcomes of LVRS in patients with pulmonary emphysema.
Key Words: emphysema • gene therapy • growth factor • lung volume reduction surgery This article has been cited by other articles:
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