Long-term post-pneumonectomy pulmonary adaptation following all-trans-retinoic acid supplementation.
In adult dogs following right pneumonectomy (PNX) and receiving all-trans-retinoic acid (RA) supplementation for 4 mo, we found modestly enhanced alveolar-capillary growth in the remaining lung without enhanced resting lung function (J Appl Physiol 96: 1080-1089 and 96: 1090-1096, 2004). Since alveolar remodeling progresses beyond this period and the lipid-soluble RA continues to be released from tissue stores, we hypothesized that RA supplementation may exert additional long-term effects. To examine this issue, adult male litter-matched foxhounds underwent right PNX followed by RA supplementation (2 mg/kg po 4 days/wk, n = 6) or placebo (n = 4) for 4 mo. Cardiopulmonary function was measured at rest and during exercise at 4 and 20 mo post-PNX. The remaining lung was fixed under a constant airway pressure for morphometric analysis. Comparing RA treatment to placebo controls, there were no differences in aerobic capacity, cardiopulmonary function, or lung volume at rest or exercise. Alveolar-capillary basal lamina thickness and mean harmonic thickness of air-blood diffusion barrier were 23-29% higher. The prevalence of double-capillary profiles remained 82% higher. Absolute volumes of septal interstitium, collagen fibers, cells, and matrix were 32% higher; the relative volumes of other septal components and alveolar-capillary surface areas expressed as ratios to control values were up to 24% higher. Thus RA supplementation following right PNX modestly and persistently enhanced long-term alveolar-capillary structural dimensions, especially the deposition of interstitial and connective tissue elements, in such a way that caused a net increase in barrier resistance to diffusion without improving lung mechanics or gas exchange.
Dept. of Internal Medicine, Pulmonary and Critical Care Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034, USA.
Priya
P
Ravikumar
D Merrill
DM
Dane
Paul
P
McDonough
Cuneyt
C
Yilmaz
Aaron S
AS
Estrera
Connie C W
CC
Hsia
D000222:Adaptation, Physiological / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D019587:Dietary Supplements; D004285:Dogs; D008168:Lung / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D011013:Pneumonectomy; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D020127:Recovery of Function / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D014212:Tretinoin / Q000008:administration & dosage*
D014212:Tretinoin