Lung hypoplasia in rats with esophageal atresia and tracheo–esophageal fistula

Survivors of esophageal atresia and tracheo–esophageal fistula (EA-TEF) often suffer chronic respiratory tract disease. EA-TEF results from abnormal emergence of the trachea from the foregut. This study in a rat model tests the hypothesis that primary lung maldevelopment might be a downstream consequence of this defect. The lung was hypoplastic in rats with EA-TEF although the histological pattern was normal. Maturation and arteriolar wall thickness were unchanged, but mesenchymal control of airway branching was weakened. This branching was deficient from embryonal day (E13) on in adriamycin-treated explants. In conclusion, the lungs were hypoplastic in rats with experimental EA-TEF due to defective embryonal airway branching. However, arteriolar wall and respiratory epithelial patterns remained normal. These findings suggest that similarly defective lung development might contribute to chronic respiratory disease in EA-TEF patients. Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle on E7, E8, and E9. Lungs were recovered at E15, E18, and E2. Lung weight/body weight ratio, total DNA and protein, radial alveolar count, arteriolar wall thickness, lung maturity, and mesenchymal control of airway branching were assessed. E13 lungs were cultured for 72 h and explant airway branching was measured daily. For comparisons, nonparametric tests (*P < 0.05) were used.