Surfactant levels after reversible tracheal occlusion and prenatal steroids in experimental diaphragmatic hernia.
OBJECTIVE
In normal lungs, fetal tracheal occlusion (TO) induces lung growth but decreases the number of type II cells; this is remedied if TO is released (TR) before delivery. In the current study, the effects of TO with or without TR on pulmonary structure and surfactant were assessed in the ovine model in which lung hypoplasia was induced by creation of a diaphragmatic hernia (CDH).


METHODS
A left-sided CDH was created in fetal lambs at 80 days gestation; TO was done at 108 days; and TR at 129 days. All ewes were given 1 dose of glucocorticoids at 135 days. At 136 days, the fetus was delivered. Lung weight to body weight ratio, mean terminal bronchiole density, type II cell density, bronchoalveolar lavage fluid (BAL) phosphatidylcholine (PC), BAL surfactant protein A (SP-A) and B (SP-B), and lung tissue SP-A and SP-B were assessed in CDH, CDH with TO, CDH with TO and TR, and controls.


RESULTS
CDH lungs were hypoplastic and structurally immature, but had increased type II cell density. TO with or without TR caused lung growth with normalization of lung parenchymal architecture and type II cell density. Although the BAL SP-A and BAL SP-B were similar in all 4 groups, the BAL PC was low in CDH with or without TO or TR. Also, lung tissue SP-B levels were low in CDH with or without TO or TR. However, lung tissue SP-A levels were normal in CDH, but low in CDH with TO with or without TR.


CONCLUSIONS
Despite the finding that lung morphology was improved in CDH with TO with or without TR animals, surfactant content and composition remained abnormal. Although surfactant secreted early by the fetus into alveolar spaces contained normal levels of BAL SP-A and BAL SP-B, the low levels of BAL PC and low lung tissue stores of SP-B indicate that these experimental lambs may experience respiratory insufficiency soon after birth. This implies that prophylactic surfactant at birth might be beneficial for CDH.
Bratu
I
I
Division of Pediatric Surgery of The Montreal Children's Hospital and the Division of Obstetrics of The Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Flageole
H
H
Laberge
J M
JM
Possmayer
F
F
Harbottle
R
R
Kay
S
S
Khalife
S
S
Piedboeuf
B
B
D000704:Analysis of Variance; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006548:Hernia, Diaphragmatic / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012756:Sheep; D014132:Trachea / Q000601:surgery*
D005938:Glucocorticoids; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D001623:Betamethasone