PRENATAL HORMONAL-THERAPY IMPROVES PULMONARY MORPHOLOGY IN RATS WITH CONGENITAL DIAPHRAGMATIC-HERNIA

The high mortality of congenital diaphragmatic hernia (CDH) is due to associated pulmonary hypoplasia, which resembles that seen in prematur e newborns with respiratory distress syndrome (RDS). By use of success ful therapies extrapolated from RDS, quantitative stereologic morphome try techniques were applied to evaluate pulmonary development followin g prenatal hormonal therapy in rats with nitrofen-induced CDH. Antenat al hormonal therapy was administered on Days 18.5 and 19.5 prior to de livery on Day 21.5 (term = Day 22), using dexamethasone (Dex), thyrotr opin-releasing hormone (TRH), Dex-TRH, or normal saline (NS) as vehicl e control. Lungs from CDH rats (n = 5) and non-nitrofen-fed controls ( n = 5) were studied, and 10 morphometric airspace parameters were dete rmined by point counting 18-30 fields/lung/animal, Indices of maturati on, including total internal surface area (SA), airspace volume fracti ons (V-Valv), duct fractions (V-Vducts), and radial alveolar count (RA G), were improved by Dex and Dex-TRH compared with NS-CDH controls (P = 0.0001), as were five other morphometric airspace parameters (P < 0. 05). Strikingly, Dex and Dex-TRH treatment corrected average airspace volume (AAV) and the volume fraction of air-conducting elements (V-Vdu cts) toward normal values seen in non-nitrofen-fed control animals. TR H therapy alone had minimal beneficial effects. Prenatal steroid +/- T RH thus improved multiple morphometric parameters of lung maturity in CDH rats, supporting the potential use of in utero hormonal therapy to treat humans with antenatally diagnosed CDH. (C) 1996 Academic Press, Inc.