Lung growth induced by prenatal tracheal occlusion and its modifying factors: A study in the rat model of congenital diaphragmatic hernia

Background/Purpose: Prenatal tracheal occlusion (TO) has been shown to acce lerate lung growth in animal models and models of pulmonary hypoplasia. How ever, these models may not mimic early events in human congenital diaphragm atic hernia (CDH). The authors previously have developed a model of TO in t he rat. The purpose of this study was to apply this technique to characteri ze TO-induced lung growth in the early onset nitrofen-induced model of CDH, and to address the clinically important questions of the effect of timing of TO and maternal infusion of terbutaline on TO-induced lung growth. Methods: Left-sided CDH was induced in the fetuses of time-dated pregnant S prague-Dawley rats by feeding 100 mg of nitrofen on day 9 of gestation. TO was performed via maternal laparotomy and hysterotomy at 19 days' gestation . At harvest (21.5 days' gestation), lungs from nitrofen-exposed fetuses wi thout CDH (non-CDH), with CDH (CDH), and with CDH and TO (CDH-TO) were comp ared by analysis of wet and dry weight, DNA and protein content, and stereo logic morphometry. A second study was performed to assess relative lung gro wth achieved by equal intervals of TO after "early" (19 days) versus "late" (20 days) gestational TO. Finally, the effect of maternal infusion of terb utaline, a commonly used tocolytic for fetal surgery, on TO-induced lung gr owth was analyzed. Results: Analysis of lung growth showed consistent and significant lung gro wth in CDH-TO lungs. Lung growth after TO was proliferative and characteriz ed by an increase in parenchymal volume as manifest by increased total sacc ular number and surface area and radial saccular count. Although visceral r eduction was partially achieved, herniated liver was reduced incompletely. The majority of lung growth occurred during the latter half of the TO perio d. Early gestational age at TO and maternal terbutaline administration adve rsely influenced lung growth in CDH-TO fetuses. Conclusions: Prenatal TO induces dramatic lung growth in the early onset, n itrofen-induced rat model of CDH. TO is more effective later in gestation p resumably because of the advanced stage of lung development and lung fluid production. This effect could be counterbalanced by the use of P-mimetic to colytic, which inhibits fetal lung fluid production late in gestation. Mult iple factors including fetal lung fluid production and absorption, pharmaco logic agents, space-occupying herniated viscera; and timing and duration of TO may be important clinical variables. The development of the rat model s hould facilitate further studies into the cellular and molecular mechanisms responsible for TO-induced lung growth. Copyright (C) 2001 by W.B. Saunder s Company.