Effect of prenatal glucocorticoids and postnatal nitric oxide inhalation on survival of newborn rats with nitrofen-induced congenital diaphragmatic hernia

Abstract

Background/purpose: Pulmonary hypertension and pulmonary hypoplasia account for the high mortality rate associated with congenital diaphragmatic hernia (CDH). In animal models of CDH, postnatal nitric oxide (NO) inhalation resulted in significantly better survival rates and antenatal glucocorticoid administration in improved lung compliance. The objective of this study was to evaluate the combined effect of prenatal glucocorticoid administration and postnatal NO inhalation on the survival rate of newborn rats with nitrofen-induced CDH.

Methods: Right-sided CDH was induced by maternal administration of a single oral dose (100 mg, intraperitoneally) of nitrofen on day 11.5 of pregnancy. Dexamethasone (DEX, 0.25 mg/kg) was given in groups III and IV by maternal intraperitoneal injection on day 18.5 and 19.5 of pregnancy. Control animals (groups I and II) received vehicle alone. After spontaneous delivery, the newborn animals were exposed to either NO (80 ppm; groups II and IV) or room air (groups I and III). Vitality (Rat-Score), sO(2) and survival were monitored continuously for 12 hours until animals were killed. Hernia size was estimated as percentage of total thoracic content.

Results: Right-sided CDH was observed in 392 of 491 newborn rats (81%). Animals with large hernias (>50%) died within 4 hours after birth, irrespective of treatment. Hernias with less than 50% of the thoracic volume were considered clinically relevant hernias. In this category, 12.5% of animals without treatment (group I) survived compared with 63.6% after NO treatment alone (group II; P <.01). Survival rate after DEX treatment alone (group III) was 69.4% (group III v I; P <.01). In group IV (DEX and NO) 95.2% of the animals survived (group IV v I; P <.001). In contrast to DEX alone, NO administration resulted in significantly better sO(2)(group II and IV) compared with group I (P <.05).

Conclusion: Combination of prenatal maternal glucocorticoids and postnatal NO inhalation significantly improved survival rate of newborn rats with nitrofen-induced CDH.