Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia: Tracheal occlusion reverses the arterial structural abnormality

Background/Purpose: The high mortality rate of congenital diaphragmatic hernia (CDH) is ascribed generally to pulmonary hypoplasia and persistent pulmonary hypertension characterized by associated pulmonary arterial structural changes. Prenatal tracheal occlusion (TO) accelerates lung growth, but the effect of TO on pulmonary arterial structure in CDH has not been well defined. The authors hypothesized that TO could reverse the pulmonary arterial structural changes observed in CDH. To address this hypothesis, we utilized the nitrofen-induced rat model of CDH to examine the effect of TO on pulmonary arterial morphology of CDH lungs. Methods: Left-sided CDH was induced by administering 100 mg of nitrofen to pregnant Sprague-Dawley rats on day 9 of gestation. TO was performed on day 19, and the fetuses were harvested on day 21.5 of gestation. After the ductus arteriosus was ligated, the pulmonary arteries were injected with a barium-gelatin mixture, and the lungs were inflation fixed. Coronal sections of the lungs were stained with elastin van Gieson. External diameter (ED), internal diameter (ID), and medial and adventitial wall thickness of the pulmonary arteries were measured using a computer image analyzer, and the percent medial thickness (%MT) and adventitial thickness (%AT) were calculated. The lungs from nitrofen-exposed fetuses with left-sided CDH (CDH group), trachea-occluded left-sided CDH (CDH+TO group), non-CDH (non-CDH group), and normal fetuses (normal group) were compared. Results: The %MT was significantly increased in all sizes of arteries in CDH compared with non-CDH and normal groups (P