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J Appl Physiol 96: 1090-1096, 2004. First published September 23, 2003; doi:10.1152/japplphysiol.00900.2002
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Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy

D. Merrill Dane,1 Xiao Yan,1 Rahul M. Tamhane,1 Robert L. Johnson, Jr.,1 Aaron S. Estrera,2 Deborah C. Hogg,1 Richard T. Hogg,1 and Connie C. W. Hsia1

Departments of 1Internal Medicine and 2Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9034

Submitted 30 September 2002 ; accepted in final form 15 August 2003

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg·kg-1·day-1 po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (Vtiss-RB) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (Vair-CT and Vtiss-CT) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas Vtiss-RB was significantly lower at both lung volumes in RA-treated animals, Vair-CT and Vtiss-CT were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

compensatory lung growth; dog; carbon monoxide diffusing capacity; nitric oxide diffusing capacity; computerized tomographic scan


Address for reprint requests and other correspondence: C. C. W. Hsia, Pulmonary and Critical Care Medicine, Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034.




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