Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy

Xiao Yan, Dennis J. Bellotto, David J. Foster, Robert L. Johnson, Herbert K. Hagler, Aaron S. Estrera, Connie C W Hsia

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1080-1089
Number of pages10
JournalJournal of Applied Physiology
Volume96
Issue number3
DOIs
StatePublished - Mar 2004

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Pneumonectomy
Tretinoin
Growth
Lung
Endothelial Cells
Placebos
Lung Volume Measurements
Alveolar Epithelial Cells
Fixatives
Cell Size
Therapeutics
Gases
Dogs
Pressure

Keywords

  • Alveolar capillary growth
  • Compensatory lung growth
  • Dog
  • Endothelial cell volume
  • Lung morphometry

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy. / Yan, Xiao; Bellotto, Dennis J.; Foster, David J.; Johnson, Robert L.; Hagler, Herbert K.; Estrera, Aaron S.; Hsia, Connie C W.

In: Journal of Applied Physiology, Vol. 96, No. 3, 03.2004, p. 1080-1089.

Research output: Contribution to journalArticle

Yan, Xiao ; Bellotto, Dennis J. ; Foster, David J. ; Johnson, Robert L. ; Hagler, Herbert K. ; Estrera, Aaron S. ; Hsia, Connie C W. / Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy. In: Journal of Applied Physiology. 2004 ; Vol. 96, No. 3. pp. 1080-1089.
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abstract = "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.",
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