Pulmonary structural maturation and pulmonary artery remodeling after reversible fetal ovine tracheal occlusion in diaphragmatic hernia.
OBJECTIVE
Congenital diaphragmatic hernia (CDH) is associated with thickened pulmonary arteries (PA) contributing to pulmonary hypertension. In the current study, the effects of antenatal glucocorticoids and reversible tracheal occlusion (TO) on PA structure were assessed in a hypoplastic lung model.


METHODS
A left-sided CDH was created in fetal lambs at 80 days gestation, TO at 108 days, and release of the occlusion (TR) at 129 days. All were given 1 dose of maternal glucocorticoids at 135 days. At 136 days (term, 145 days), the fetus was delivered by cesarian section. CDH (n = 7), CDH + TO (n = 6), CDH + TO + TR (n = 6), and unoperated twin controls (n = 16) were compared. Outcome measurements were (1) lung growth, represented by lung weight to body weight ratio (LW/BW), (2) lung structural maturation, which is inversely proportional to mean terminal bronchiole density (MTBD), (3) PA medial and adventitial areas (square micrometers), (4) lung capillary load, which is the ratio of vessel surface area (SA) to tissue SA ratio.


RESULTS
CDH lungs were hypoplastic with a low LW/BW and high MTBD. The small PAs (<75 microm) of CDH had an increased medial area, indicating increased muscle mass and an increased adventitial area. CDH + TO +/- TR increased LW/BW and achieved normal structural lung maturity with a low MTBD. Only CDH + TO thinned the PA medial area closer to control values. The adventitial area remained thick in CDH +/- TO +/- TR when compared with controls. All 4 groups had similar capillary load.


CONCLUSIONS
TO may be especially important for PA remodeling in the latter part of gestation, because TR 1 week before delivery prevents thinning of the small PAs in CDH. The shaping achieved by TO in terms of lung growth, structural maturity, and pulmonary artery medial area thinning may prove beneficial in lessening the severity of the associated pulmonary hypertension in CDH.
Bratu
I
I
Division of Pediatric Surgery of The Montreal Children's Hospital; the Division of Pathology of The Royal Victoria Hospital, McGill University, Montreal, Quebec; Canada.
Flageole
H
H
Laberge
J M
JM
Chen
M F
MF
Piedboeuf
B
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D021721:Balloon Occlusion / Q000295:instrumentation / Q000379:methods*; D001623:Betamethasone / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005315:Fetal Diseases / Q000401:mortality / Q000628:therapy*; D005325:Fetal Organ Maturity; D005865:Gestational Age; D005938:Glucocorticoids / Q000627:therapeutic use*; D006548:Hernia, Diaphragmatic / Q000401:mortality / Q000628:therapy*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects* / Q000254:growth & development; D009929:Organ Size; D010547:Persistent Fetal Circulation Syndrome / Q000401:mortality / Q000628:therapy*; D011295:Prenatal Care / Q000379:methods*; D011651:Pulmonary Artery / Q000002:abnormalities* / Q000187:drug effects* / Q000254:growth & development; D012756:Sheep; D016019:Survival Analysis; D014132:Trachea; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D001623:Betamethasone