Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy.
To determine whether all-trans retinoic acid (RA) enhances compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x 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.
Yan
Xiao
X
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9034, USA.
Bellotto
Dennis J
DJ
Foster
David J
DJ
Johnson
Robert L
RL
Hagler
Herbert K
HK
Estrera
Aaron S
AS
Hsia
Connie C W
CC
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D004285:Dogs; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000254:growth & development; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D011013:Pneumonectomy / Q000379:methods / Q000706:statistics & numerical data; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin