Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.
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 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 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-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 V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-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.
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D011013:Pneumonectomy / Q000379:methods / Q000706:statistics & numerical data; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin