title: Lung hypoplasia can be reversed by short-term obstruction of the trachea in fetal sheep.
abstract: Our aim was to determine whether an existing lung growth deficit could be reversed, in utero, by short-term (6 d) obstruction of the fetal trachea. Chronically catheterized fetal sheep (term approximately 145 d) were divided into four groups: 1) no treatment (control); 2) continuous lung liquid drainage to induce lung hypoplasia (105-134 d, drain); 3) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by restoration of tracheal flow (128-134 d, drain and reconnect); and 4) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by tracheal occlusion to accelerate lung growth (128-134 d, drain and obstruct). Lung liquid volumes and secretion rates were measured on d 125, 130, and 134 of gestation and postmortem data collected on d 135. Compared with controls, continuous lung liquid drainage (drain) significantly reduced wet lung weights (34.3 +/- 2.6 g/kg versus 13.3 +/- 1.4 g/kg) and total lung DNA contents (177 +/- 11 mg/kg versus 94 +/- 7 mg/kg). Reestablishing tracheal flow for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 +/- 1.6 g/kg), but not total DNA contents (106 +/- 9 mg/kg), compared with lung liquid drained fetuses (drain). After 6 d of tracheal obstruction (drain and obstruct) lung liquid volumes, wet lung weights, and total protein contents (weight, 28.6 +/- 2.8 g/kg; protein, 1376 +/- 97 mg/kg) were similar to control values (weight, 34.3 +/- 2.6 g/kg; protein, 1506 +/- 123 mg/kg); lung DNA contents were less than control but greater than values from lung liquid drained fetuses (drain and obstruct, 140 +/- 9 mg/kg versus drain, 94 +/- 7 mg/kg). We conclude that obstruction of the trachea can reverse an existing fetal lung growth deficit in approximately 6 d, whereas merely restoring tracheal continuity does not increase fetal lung growth.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Nardo
authors.forename: S B
authors.initials: SB
authors.lastname: Hooper
authors.forename: R
authors.initials: R
authors.lastname: Harding
mesh_terms: D000402:Airway Obstruction; D000818:Animals; D001826:Body Fluids; D002417:Cattle; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control* / Q000601:surgery; D008168:Lung / Q000002:abnormalities* / Q000196:embryology; D009929:Organ Size; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D012756:Sheep; D014132:Trachea / Q000196:embryology / Q000601:surgery*
chemical_list: D011506:Proteins; D004247:DNA