Tracheobronchial malformations in experimental esophageal atresia

Malformations of the tracheobronchial tree may account for postoperative respiratory symptoms in patients with esophageal atresia (EA). This study examines the respiratory tract in fetal rats with EA induced by Adriamycin.

Time-mated female rats were given either 2 mg/kg intraperitoneal Adriamycin on gestational days 8 and 9 (adria group, n = 6) or no treatment (control group, n = 2), and the fetuses were recovered on day 21. Laryngo-tracheo bronchial tree was studied after transparentation and alcian blue-alizarin red staining that depicts the cartilage in blue and make the surrounding tissues transparent.

There were no malformations in any of the 1 1 control animals studied. Conversely, 31 of 46 (67%) Adriamycin fetuses had EA with distal TEF. These had more tracheal rings than controls (32+/-2 v 26+/-1.5, P < .05) at the expense of those of the mainstem bronchi (3.2+/-1 v 6.6+/-1.1 in the right, P< .05 and 6.2+/-2.1 v 11+/-1.1 in the left, P < .05). There were tracheal stenoses in 16 pups with EA (some severe and five double), and all these had fragmented rings in the trachea or bronchi. In six cases there was an ectopic upper right bronchus, and 1 had a grossly abnormal larynx. The malformations in the 15 Adriamycin-exposed fetuses without EA were limited to some fragmented or mishaped rings.

Laryngo-tracheobronchial malformations entailing the whole length of the tract are very constant and severe in rats with EA and tracheoesophageal fistula and correspond to an abnormal development of the tracheobronchial anlage from the ventral foregut. Their nature and extent invite a careful investigation of the respiratory tracts in EA babies in whom they could be underscored.