PRENATAL HORMONAL-THERAPY IMPROVES PULMONARY COMPLIANCE IN THE NITROFEN-INDUCED CDH RAT MODEL

Neonates with congenital diaphragmatic hernia (CDH) experience a high mortality despite intensive medical and surgical management. The assoc iated pulmonary hypoplasia is accompanied by an underlying biochemical deficiency that bears similarity to respiratory distress syndrome (RD S) in the premature newborn. Using therapies extrapolated from those u sed to treat RDS, the authors have previously shown correction of the immature pulmonary biochemical indices in the nitrofen rat CDH model. This study investigates the functional and histological outcome of pre natal hormone therapy on CDH rats. Compared with saline-treated CDH co ntrols, dexamethasone-treated CDH animals achieved significant Increas es in lung distensibility (P = .0006) and functional residual capacity (P = .004); CDH rats treated with combined dexamethasone and thyrotro pin-releasing hormone (TRH) showed improved functional residual capaci ty (p = .043) and alveolar stability (P = .025); CDH animals treated w ith TRH alone (TRH-CDH) showed no improvement in any parameter tested. Histologically, the lungs from dexamethasone- and dexamethasone-TRH-t reated CDH animals showed changes that included narrow septal walls, i ncreased air saccule size, and thinning of the pulmonary interstitium compared with the lungs of saline or TRH-CDH rats, which were developm entally arrested at the canalicular State. Lung weights and lung weigh t-body weights ratios were similar in all CDH rats, confirming that tr eatment did hbt impair pulmonary growth. These results support the pot ential clinical use of prenatal pharmacological therapies to treat hum an fetuses with prenatally diagnosed CDH. Copyright (C) 1995 by W.B. S aunders Company