The Effect of Tracheal Occlusion on Lung Branching in the Rat Nitrofen CDH Model

BACKGROUND: Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia (CDH). TO increases lung size, but it is unclear whether TO stimulates mature lung growth or simply induces alveolarization without concomitant bronchial development. In this study, we characterize bronchial branch development in fetal rats with CDH with or without TO through conventional histological and morphometric analysis as well as lung casting. MATERIALS AND METHODS: Rat dams were gavaged nitrofen at gestational day 9.5, and 3 to 4 fetuses per dam underwent fetal TO on gestational day 19 (term = 22 days). Fetuses were sacrificed on day 21, the presence of CDH was confirmed, and the lung weight to body weight ratio (LW/BW) was calculated. Lung casts of all research groups were created using liquid silicon and bronchial branches were quantified from lung periphery to carina. RESULTS: CDH fetuses had smaller LW/BW ratios and a lesser percentage (%) of airspace when compared to controls, and manifested less lung branching than controls. Fetuses treated by TO had a greater LW/BW ratio and % airspace, but did not have a different number of branch iterations. Fetuses with CDH and TO demonstrated a restoration in LW/BW ratio to control levels (P = 0.42), but the number of bronchial branch iterations remained less than control animals. CONCLUSION: The results of this study suggest that TO in this animal model at gestational day 19 promotes distal airway proliferation but does not reverse the underdevelopment of bronchial branching seen in lung hypoplasia due to CDH.