Tracheal occlusion in the fetal rat: A new experimental model for the study of accelerated lung growth

Background: Prenatal tracheal occlusion accelerates fetal lung growth, but the mechanism of this phenomenon is unknown. Previous animal models have be en limited by expense, lack of species-specific molecular probes, or the st age of lung development when studies could be performed. To provide a model that is more amenable to systematic analysis, we have developed an in vivo rat model of prenatal tracheal occlusion. Methods: Time-dated pregnant rats underwent laparotomy at 19 days' gestatio nal age (term, 22 days). The fetal head and neck were exteriorized through a hysterotomy, and the trachea was ligated under a dissecting microscope. T he fetus was returned to the amniotic cavity, and the uterine and maternal abdominal incisions were closed. The dam and the fetuses were killed at 21. 5 days' gestational age, and the fetal lungs were assessed for lung growth and compared with nonoperated littermate controls. Results: Thirty-two of 50 manipulated fetuses survived. Of the 32 survivors , successful tracheal ligation was confirmed in 20, and these 20 fetuses we re compared with 33 littermate controls. Fetal body weight (4.81 +/- 0.26 g v 4.87 +/- 0.41 g) and heart weight (0.05 +/- 0.01 g v 0.05 +/- 0.01 g) we re not significantly different between ligated fetuses and littermate contr ols, whereas the wet lung weight (0.30 +/- 0.06 g v 0.13 +/- 0.02 g, P<.01) , lung-to-body-weight ratio (6.34 +/- 1.16% v 2.64 +/- 0.41%, P<.01), dry l ung weight (17.4 +/- 2.45 mg v 12.1 +/- 1.87 mg, P<.01), total lung DNA (12 10 +/- 371 mu g v 828 +/- 208 mu g, P <.01), and total lung protein (14.3 /- 5.3 mg v 8.7 +/- 1.7 mg, P <.01) were increased significantly in the lig ated fetuses. The enlarged lung demonstrated normal histology findings afte r inflation fixation. Conclusions: Prenatal tracheal occlusion during the canalicular stage of lu ng development accelerates lung growth in the rat. In comparison with other large animal models, this relatively inexpensive small animal model has th e distinct advantages of a short gestation, a large number of fetuses per l itter, the availability of a developmental model of congenital diaphragmati c hernia, and the availability of well-defined molecular probes to investig ate the mechanism of tracheal occlusion-induced lung growth. J Pediatr Surg 33:1741-1744. Copyright (C) 1998 by W.B. Saunders Company.