Effects of mechanical factors on growth and maturation of the lung in fetal sheep. Joe, P., L. D. Wallen, C. J. Chapin, C. H. Lee, L. Allen, V. K. M. Han, L. G. Dobbs, S. Hawgood, and J. A. Kitterman. Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco, and the Lawson Research Institute, London, Ontario, Canada
APStracts 3:0153L, 1996.
Previous fetal studies indicated that endocrine factors control surfactant maturation whereas mechanical forces affect lung growth, but not surfactant. We altered mechanical forces in fetal sheep lungs at 100-108d gestation by tracheal ligation (TL, n=15, 7 successful studies) to accelerate lung growth, transection of cervical spinal cord (TCSC, n=17, 6 successful studies) to produce lung hypoplasia, or sham operation (n=11, 6 successful studies). The reasons for the high mortality rates are not known. At delivery (130-142d), groups were similar in gestational age, weight and cortisol. Effects on lung growth were similar to, but effects on surfactant differed from, previous reports. TL increased lung growth but decreased saturated phosphatidylcholine (SatPC), surfactant protein A (SP-A) and apparently decreased SP-B and relative numbers of alveolar type II cells (based on immunohistochemical studies of 1 animal in each group); TCSC had opposite effects. In contrast to a previous study (J Appl Physiol 51:384, 1981), SatPC did not correlate with cortisol. We conclude that altering mechanical forces in fetal lung affects not only lung growth but also surfactant maturation and possibly alveolar epithelial differentiation and disturbs the normal correlation between cortisol and surfactant. Associated changes in insulin-like growth factor I (IGF-I; increased by TL, P=0.003) suggest a possible role of IGF-I in these effects. 

Received 21 February 1996; accepted in final form 29 August 1996.
APS Manuscript Number L57-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996