Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

Abstract

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF_1α), thromboxane A₂ (TxB₂), prostaglandin E₂ (PGE₂), and leukotriene B₄ (LTB₄) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF_1α, reflecting the pulmonary vasodilator prostacyclin (PGI₂), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF_1α in CDH may reflect a compensation mechanism for increased vascular resistance.