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Lack of response to all-trans retinoic acid supplementation in adult dogs following left pneumonectomy

Departments of ¹Internal Medicine, ²Pathology, and ³Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas

Submitted 10 May 2005 ; accepted in final form 12 June 2005

We showed previously that removing 55–58% of the lung by right pneumonectomy (R-PNX) in adult dogs triggers compensatory growth of the remaining lung, but removing 42–45% of the lung by left PNX (L-PNX) does not. We also showed that, following R-PNX, supplemental all-trans retinoic acid (RA) selectively enhances alveolar capillary endothelial cell volume (Yan X, Bellotto DJ, Foster DJ, Johnson RL, Jr., Hagler HH, Estrera AS, and Hsia CC. J Appl Physiol 96: 1080–1089, 2004). We hypothesized that RA supplementation might enhance compensation following L-PNX and tested this hypothesis by administering RA (2 mg·kg^–1·day^–1, 4 days/wk) or placebo orally to litter-matched adult foxhounds for 4 mo following L-PNX. Resting lung function was measured under anesthesia. Air and tissue volumes of the remaining lung were assessed by high-resolution computed tomography scan and by detailed postmortem morphometric analysis of the fixed lung. There was no significant difference in resting lung function, lung volume, alveolar structure, or septal ultrastructure between RA and placebo treatment groups. We conclude that RA supplementation does not induce post-PNX compensatory lung growth in the absence of existing cellular growth activities initiated by other primary signals.

compensatory lung growth; lung resection; alveolar capillary surface area; lung diffusing capacity; high-resolution computed tomography; lung morphometry

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