Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy

• Published in: Journal of applied physiology (1985) 2004-03, Vol.96 (3), p.1080-1089
• Main Authors: Yan, Xiao, Bellotto, Dennis J, Foster, David J, Johnson, Robert L., Jr, Hagler, Herbert K, Estrera, Aaron S, Hsia, Connie C. W
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood vessels; Capillaries - drug effects; Capillaries - growth & development; Dogs; Fundamental and applied biological sciences. Psychology; Lung - blood supply; Lung - drug effects; Lung - growth & development; Lung Volume Measurements - methods; Lungs; Male; Pneumonectomy - methods; Pneumonectomy - statistics & numerical data; Pulmonary Alveoli - blood supply; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - growth & development; Pulmonary Diffusing Capacity - drug effects; Pulmonary Diffusing Capacity - physiology; Respiratory system; Tretinoin - pharmacology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00771.2003

Departments of 1 Internal Medicine, 2 Pathology, and 3 Cardiovascular 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.