CHANGES IN LUNG EICOSANOID CONTENT DURING NORMAL AND ABNORMAL TRANSITION IN PERINATAL LAMBS

To study the potential contribution of eicosanoids in maintaining high vascular tone in utero or in modulating resistance during the normal or abnormal transition of the pulmonary circulation, we performed serial measurements of hemodynamic parameters and lung eicosanoid content in perinatal sheep with and without pulmonary hypertension. Prostacyclin (6-keto-PGF1-alpha), thromboxane (TxB2), and leukotriene contents were measured in fetal lung liquid (FLL), bronchoalveolar lavage fluid (BALF), and lung tissue samples. Leukotriene content was barely detectable above background in FLL samples from 11 late-gestation fetuses, and lung leukotriene content in fetal lung was one-third of that measured in maternal lung (P < 0.01). Tissue samples from serial lung biopsies obtained before and after cesarean-section delivery of late-gestation lambs demonstrated increased lung prostacyclin content after delivery (P < 0.04), but no changes in total leukotriene or thromboxane contents were found. In an experimental model of perinatal pulmonary hypertension, prostanoid and leukotriene content of FLL obtained immediately before delivery were not different from an age-matched nonhypertensive control group. Leukotriene content in BALF and lung tissue obtained 2 h after delivery was not increased in the hypertensive group. TxB2, but not 6-keto-PGF1-alpha, content was higher in lung tissue from the hypertensive group (P < 0.02). Thus lung leukotriene content did not decrease from fetal values after cesarean-section delivery, and the lipoxygenase pathway was not significantly activated with delivery after chronic intrauterine pulmonary hypertension. These findings do not support the hypothesis that leukotrienes contribute significantly to elevated pulmonary vascular resistance in the normal fetus or in an experimental model of the failure of postnatal adaptation.