STIMULATION OF LUNG GROWTH BY TRACHEAL OBSTRUCTION IN FETAL SHEEP - RELATION TO LUMINAL PRESSURE AND LUNG LIQUID VOLUME

Obstruction of the fetal trachea causes liquid to accumulate within th e future airways, which is a potent stimulus for lung growth. Our aim was to determine the relationship between the increase in fetal lung g rowth after tracheal obstruction and the increases in lung liquid volu me and tracheal pressure to better understand the mechanisms involved in the growth response. The effects of 4 and 10 d of tracheal obstruct ion on lung DNA and protein contents and DNA synthesis rates were dete rmined; these data were combined with data collected previously after 2 and 7 d of tracheal obstruction. Fetal lung liquid volumes and secre tion rates were measured before (d 0) and on d 1, 2, 4, 7, and 10 afte r tracheal obstruction; fetal tracheal pressures were monitored throug hout this period. Tracheal pressures increased from 2.9 +/- 0.8 mm Hg (control) to 4.3 +/- 0.4 mm Hg within 1 d of tracheal obstruction and remained at this elevated level for the duration of the obstruction pe riod. Lung liquid volume increased progressively from 24.7 +/- 1.1 mL/ kg on d 0 to 97.3 +/- 15.2 mL/kg at d 7 of tracheal obstruction, but h ad not increased further by d 10. Tracheal obstruction significantly i ncreased lung DNA and protein contents above control values; over the 10-d period the increase in lung DNA content was closely related (r = 0.99) to the increase in lung liquid volume, but not to the increase i n tracheal pressure. DNA synthesis rates were increased at 4 d of trac heal obstruction (by 66%) but had returned to control levels by d 10. We conclude that: 1) the mechanisms responsible for the acceleration i n lung growth induced by tracheal obstruction are most active on d 2, remain active at a reduced level on d 4 and 7, and have returned to co ntrol levels by d 10; and 2) the increase in lung DNA content during t racheal obstruction (d 2-7) is closely related to the increase in lung liquid volume, but not to the increase in intraluminal pressure. Thus , we suggest that an increase in lung expansion is one of the primary factors responsible for the acceleration in fetal lung growth induced by tracheal obstruction.