A New Rodent Experimental Model of Esophageal Atresia and Tracheoesophageal Fistula: Preliminary Report

In spite of the interest paid by pediatric surgeons to esophageal atresia (EA) with tracheoesophageal fistula (TEF), no animal experimental model has been available for investigation. This preliminary report describes a reproducible fetal model of these malformations. Time-mated pregnant rats were given 1.5, 1.75, or 2 mg/kg of Adriamycin intraperitoneally on days 6 to 9 of gestation, and the litters were recovered on day 21 (near full-term). The amount of amniotic fluid was measured, and the fetuses were dissected and studied histologically. The findings were compared with those of suitable control fetuses. Adriamycin-exposed fetuses weighed less than controls. EA with TEF (Gross' type C) was found in 28%, 45%, and 41% of animals in the three dose groups (respectively). The malformation was anatomically identical to that of the human neonate, and the amount of amniotic fluid in affected fetuses increased significantly. In one instance, an H-type fistula was observed. In addition to esophageal interruption, many other malformations fitting within the human VATER association were found: duodenal atresia (41%, 50%, and 47%, respectively), anorectal (28%, 50%, and 41%), renal (81%, 100%, and 100%), and limb malformations (0%, 2.3%, and 13.8%). This new, easily reproducible and relatively inexpensive experimental model of one of the most interesting pediatric surgical malformations permits new research into both its embryogenesis and the biology of the malformed fetus.