Use of antenatal steroids to counteract the negative effects of tracheal occlusion in the fetal lamb model.
Tracheal occlusion (TO) in fetal lambs induces pulmonary hyperplasia but has negative effects on type II cells. The purpose of this study was to determine whether antenatal steroids could reverse the adverse effects of TO on lung maturation in fetal lambs. Sixteen time-dated pregnant ewes (term, 145 d) and 24 of their fetuses were divided into six groups: 1) TO at 117 d gestation; 2) TO at 117 d with a single maternal intramuscular injection of 0.5 mg/kg betamethasone 24 h before delivery; 3) TO at 117 d and release of the occlusion 2 d before delivery; 4) TO and release of the occlusion with maternal steroids; 5) unoperated controls without antenatal steroid treatment; and 6) unoperated controls, littermates of groups 1-4, treated with antenatal steroids. All fetuses were killed at 137 d gestation. Outcome measurements consisted of lung weight-to-body weight ratio; lung morphometry determined by mean terminal bronchial density; and assessment of type II pneumocytes by in situ hybridization to the mRNA of surfactant proteins B and C. Lung weight-to-body weight ratio and mean terminal bronchial density were significantly different among groups with TO and controls, indicating increased lung growth and structural maturation. The density of type II pneumocytes was markedly decreased by TO. Release 2 d before sacrifice significantly increased the density and surfactant activity of type II pneumocytes, but to levels still far from controls. Steroids alone had an effect similar to release. An additive effect was noted with steroids and 2-d release resulting in type II cell density comparable to controls. After fetal TO, a single maternal intramuscular dose of 0.5 mg/kg of betamethasone 24 h before delivery allows partial recuperation of the type II pneumocytes, an effect that is potentiated by 2-d release.
Kay
S
S
The Montreal Children's Hospital, Department of Surgery, McGill University, Montreal, Quebec H3H 1P3, Canada.
Laberge
J M
JM
Flageole
H
H
Richardson
S
S
Belanger
S
S
Piedboeuf
B
B
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017403:In Situ Hybridization; D011247:Pregnancy; D011510:Proteolipids / Q000235:genetics; D011663:Pulmonary Surfactants / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012756:Sheep / Q000196:embryology*; D013256:Steroids / Q000627:therapeutic use*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D013256:Steroids