Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy

Abstract

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-1po 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-CTand 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-RBwas significantly lower at both lung volumes in RA-treated animals, Vair-CTand Vtiss-CTwere 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.