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(Circulation. 2002;106:I-120.)
© 2002 American Heart Association, Inc.

Thoracic Transplantation and Mechanical Support for Congestive Heart Failure

Keratinocyte Growth Factor Enhances Post-Pneumonectomy Lung Growth by Alveolar Proliferation

Aditya K. Kaza, MD; Irving L. Kron, MD; Shari M. Leuwerke, MS; Curtis G. Tribble, MD; Victor E. Laubach, PhD

From the Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia Health System, Charlottesville, Va.

Correspondence to Victor E. Laubach, PhD, University of Virginia Health System, Department of Surgery, Box 801359, Charlottesville, VA 22908-1359. E-mail: vel8n{at}virginia.edu

Abstract

Background Keratinocyte growth factor (KGF) has been shown to play an important role in pneumocyte proliferation and lung development. We hypothesized that exogenous KGF would enhance postpneumonectomy compensatory lung growth through alveolar proliferation.

Methods and Results Adult Sprague–Dawley rats were used. Left pneumonectomy was performed in group P, sham thoracotomy in group S, and left pneumonectomy with administration of KGF (6.25 mg/week, intraperitoneally) in group PK. Lung weight index (LWI), lung volume index (LVI), and alveolar cell proliferation index (CPI) were measured in the right lung at 10 and 21 days after surgery. Morphometric analysis was used to determine alveolar surface density (Sv) and total volume of respiratory region (TVvr). As expected, LWI, LVI, and CPI were significantly increased after pneumonectomy at both time points in group P. The administration of KGF resulted in further significant enhancements of LWI, LVI, and CPI in group PK. TVvr was significantly increased in group P and further enhanced in group PK. Interestingly, Sv was not altered in group P but was significantly elevated in group PK. Administration of KGF to sham-operated animals did not alter LWI, LVI, or CPI.

Conclusions KGF enhances compensatory lung growth after pneumonectomy in adult rats as indicated by increased LWI, LVI, and CPI. KGF induces new alveolar formation, as indicated by increases in Sv and TVvr. We believe that this is the first evidence that KGF can induce new alveolar formation in mature lungs.

Key Words: lung • growth factors • surgery • transplantation