Prenatal dexamethasone rescues heart hypoplasia in fetal rats with congenital diaphragmatic hernia

Background/Purpose: Patients and rats with congenital diaphragmatic hernia (CDH) have lung and heart hypoplasia. Prenatal steroids improve lung hypopl asia in CDH rats. The current study tests the hypothesis that prenatal dexa methasone could rescue heart hypoplasia in rats with CDH. Methods: Timed pregnant rats received intragastrically either 100 mg nitrof en or oil on day 9.5, and other animals had the same treatment with, in add ition, either 0.25 mg/kg dexamethasone intraperitoneally or no treatment on days 19 and 20. Fetuses were recovered on day 21, and heart weight to body weight ratios, heart DNA, protein, and glycogen were measured in fresh spe cimens. Left-to-right ventricular diameter and aortic-to-pulmonary diameter ratios were measured after formalin fixation. Results: Wet heart weight to body weight, left-to-right ventricular diamete r, and aortic-to-pulmonary root diameter ratios, which were lower in fetuse s exposed only to nitrofen than in their oil controls, were similar in thos e exposed to nitrofen plus dexamethasone than in their corresponding oil pl us dexamethasone controls. Total heart DNA, which was decreased in fetuses exposed to nitrofen with CDH in comparison with their controls, was increas ed in those receiving nitrofen and dexamethasone in comparison with theirs. Protein to DNA ratio was decreased in all rats with CDH irrespective of th eir exposure or not to dexamethasone. Glycogen to DNA ratio was higher in a ll dexamethasone-treated fetuses than in those without this treatment. No g ross histologic differences were seen among groups. Conclusions: Heart hypoplasia in rats with CDH is in part rescued by prenat al dexamethasone treatment as expressed by increased number of smaller myoc ytes with higher glycogen content. Prenatal steroids could modify heart inv olvement in human fetuses with CDH as well. J Pediatr Surg 35:1757-1767. Co pyright (C) 2000 by W.B. Saunders Company.