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J Appl Physiol 96: 1080-1089, 2004. First published November 14, 2003; doi:10.1152/japplphysiol.00771.2003
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Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy

Xiao Yan,1 Dennis J. Bellotto,2 David J. Foster,1 Robert L. Johnson, Jr.,1 Herbert K. Hagler,2 Aaron S. Estrera,3 and Connie C. W. Hsia1

Departments of 1Internal Medicine, 2Pathology, and 3Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9034

Submitted 24 July 2003 ; accepted in final form 20 October 2003

To determine whether all-trans retinoic acid (RA) enhances 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 4 mo, the remaining lung was fixed by tracheal instillation of fixatives at a constant airway pressure for detailed morphometric analysis. After RA treatment compared with placebo, lung volume was slightly but not significantly lower. Volume density of septum to lung was 37% higher because of a 50 and 25% higher volume density of capillary and septal tissue, respectively. Mean septal thickness was 27% higher. Absolute volumes of endothelial cells and capillary blood were 31-37% higher, whereas epithelial and interstitial volumes were not different between groups. Absolute alveolar-capillary surface areas did not differ between groups, and alveolar septal surface-to-volume ratio was 20% lower in RA-treated animals. RA treatment exaggerated interlobar differences in morphometric indexes and caused alveolar capillary morphology to revert to a more immature state. Thus RA treatment during early post-R-PNX adaptation preferentially enhanced alveolar capillary and endothelial cell volumes consistent with formation of new capillaries, but the associated septal distortion precluded a corresponding increase in gas-exchange surface or morphometric estimates of lung diffusing capacity.

compensatory lung growth; dog; lung morphometry; endothelial cell volume; alveolar capillary growth


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




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