LEUKOTRIENES AND PROSTAGLANDINS IN FETAL LUNG LIQUID

Several recent studies have suggested that peptidoleukotrienes are involved in or responsible for the pulmonary pressor response to hypoxia as well as the normally high pulmonary vascular resistance of fetal lambs. The present studies were carried out to test these hypotheses. Fetal lambs were prepared with indwelling vascular catheters and tracheal catheters for access to lung liquid. We measured lung liquid levels of leukotrienes C4 (LTC4) and D4 (LTD4) in control unanesthetized fetal lambs with blood gases and pH in the normal range. In the control series, LTC4 and LTD4 were either not detectable or their levels were close to the limit of resolution (LTC4, < 80 pg/ml; LTD4, < 50 pg/ml) of the techniques utilized. Leukotriene E4 was measured in a separate study by using pooled samples, and it was also found to be below the detection limit of that assay (10 pg/ml). In a second series of animals, a level of acute hypoxia was induced to decrease fetal arterial PO2 to 12 Torr for 20 min. After hypoxia, tracheal fluid levels of leukotrienes were again below detection limits of the assays used (LTC4, < 80 pg/ml; LTD4, < 142 pg/ml). In another study, methodology was altered to lower the detection limits of leukotrienes in lung fluid and to allow the measurement of total peptidoleukotriene concentrations. In this study, even when hypoxia was extended for up to 1 h, leukotriene levels were consistently below the limit of detection of the assay (< 20 pg/ml for the sum of all leukotrienes). The prostanoids 6-ketoprostaglandin F(1α) and thromboxane B2 were also measured and found to be unaffected by prolonged hypoxia. This study suggests that the normally elevated pulmonary vascular resistance of the fetus may be independent of leukotrienes. This study also suggests that leukotrienes may not be responsible for the fetal pulmonary pressor response to hypoxia.