Pd. Losty et al., PRENATAL HORMONAL-THERAPY IMPROVES PULMONARY MORPHOLOGY IN RATS WITH CONGENITAL DIAPHRAGMATIC-HERNIA, The Journal of surgical research, 65(1), 1996, pp. 42-52
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.