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1 Internal Medicine, University of Texas Southwestern Med. Ctr., Dallas, Texas, USA
2 Pathology, University of Texas Southwestern Med. Ctr., Dallas, Texas, USA
3 Cardiovascular & Thoracic Surgery, University of Texas Southwestern Med. Ctr., Dallas, Texas, USA
* To whom correspondence should be addressed. E-mail: Connie.Hsia{at}utsouthwestern.edu.
To determine if all-trans-retinoic acid (RA) enhances compensatory lung growth in fully mature animals, adult male dogs (n=4) received RA 2 mg/kg/day p.o. 4 days/wk beginning the day following 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. Following RA treatment compared to placebo, lung volume was slightly but not significantly lower. Volume density of septum to lung was 37% higher, due to 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, while 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 inter-lobar differences in morphometric indices, and caused alveolar capillary morphology to revert to a more immature state. Thus, RA treatment during early post-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.
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