Published ahead of print on March 11, 2005, doi:10.1164/rccm.200411-1518OC Am. J. Respir. Crit. Care Med., Volume 171, Number 11, June 2005, 1237-1245 A more recent version of this article appeared on June 1, 2005
Submitted on November 15, 2004 Induction of Compensatory Lung Growth in Pulmonary Emphysema Improves Surgical Outcomes in RatsNorihisa Shigemura1,1 Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, 2 Division of Molecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan, 3 Department of Gene Therapy Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan * To whom correspondence should be addressed. E-mail: n-shige{at}blue.ocn.ne.jp.
Rationale and Objectives: Although lung volume reduction surgery (LVRS) has been widely employed 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 following 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 following 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 following LVRS may be a new strategy to further improve clinical outcomes of LVRS in patients with pulmonary emphysema. Key words: emphysema; lung volume reduction surgery; gene therapy; growth factor
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