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 the future airways, which is a potent stimulus for lung growth. Our aim was to determine the relationship between the increase in fetal lung growth after tracheal obstruction and the increases in lung liquid volume and tracheal pressure to better understand the mechanisms involved in the growth response. The effects of 4 and 10 d of tracheal obstruction on lung DNA and protein contents and DNA synthesis rates were determined; these data were combined with data collected previously after 2 and 7 d of tracheal obstruction. Fetal lung liquid volumes and secretion rates were measured before (d 0) and on d 1, 2, 4, 7, and 10 after tracheal obstruction; fetal tracheal pressures were monitored throughout 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 period. 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 had not increased further by d 10. Tracheal obstruction significantly increased 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 in tracheal pressure. DNA synthesis rates were increased at 4 d of tracheal obstruction (by 66%) but had returned to control levels by d 10. We conclude that: 1) the mechanisms responsible for the acceleration in 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 control levels by d 10; and 2) the increase in lung DNA content during tracheal 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.