title: Lung morphology after late fetal tracheal ligation in rats.
abstract: Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in congenital diaphragmatic hernia (CDH). Prenatal tracheal occlusion accelerates lung growth, but the mechanism remains unknown. In order to be able to establish the accuracy of our experimental model for further molecular biological examinations, we evaluated the histologic structure of 1. fetal lungs subjected to tracheal occlusion compared to 2. normal fetal lungs, 3. hypoplastic lungs in CDH, and 4. normal neonatal lungs. One group of Sprague-Dawley rat fetuses were subjected to intrauterine tracheal ligation (TL) on gestational day 19 (n = 7). Control fetuses were obtained from the same litters as those subjected to TL (n = 8). Another group of pregnant Sprague-Dawley rats were given 100 mg nitrofen on gestational day 9.5 to create CDH (n = 8). All fetuses were delivered by cesarean section on day 21. Lungs from 1-day-old, healthy, non-operated, newborn Sprague-Dawley rats were also examined (n = 6). Lung weight to body weight ratio was significantly higher in the TL lungs (5.0 +/- 0.36 %), compared to control lungs (2.8 +/- 0.15 %), CDH lungs (1.9 +/- 0.12 %), and normal neonatal lungs (4.2 +/- 0.18 %). Volume density of alveolar air space and radial alveolar count (RAC) in TL lungs (52 +/- 1.4 %) (3.3 +/- 0.25) were significantly higher than in control lungs (34 +/- 3.4 %) (2.2 +/- 0.17) and in CDH lungs (16 +/- 1.7 %) (1.7 +/- 0.07). No significant differences were found between the TL and the normal neonatal group (59 +/- 1.4 %) (3.6 +/- 0.11). Fetal lungs after TL showed evidence of growth stimulation with increased volume density of alveolar air space and increased RAC, comparable to findings in normal neonatal lungs.
authors.affiliation: Department of Pediatric Surgery, Karolinska Institutet, Stockholm, Sweden. Carmen.mesas.burgos@ki.se
authors.forename: C
authors.initials: C
authors.lastname: Mesas-Burgos
authors.forename: A-C
authors.initials: AC
authors.lastname: Eklöf
authors.forename: B
authors.initials: B
authors.lastname: Linderholm
authors.forename: B
authors.initials: B
authors.lastname: Robertson
authors.forename: B
authors.initials: B
authors.lastname: Frenckner
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D006548:Hernia, Diaphragmatic / Q000473:pathology*; D065630:Hernias, Diaphragmatic, Congenital; D008026:Ligation; D008168:Lung / Q000196:embryology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea