The effect of indomethacin treatment of the pulmonary vasodilation caused by ventilation of the fetal lung with air was evaluated in anesthetized, exteriorized, fetal goats by means of an open-chest, pump-perfused lung preparation. The decrease in pulmonary vascular resistance that occurs when the fetal lung is ventilated with air consists of two components: 1) a rapid decrease in pulmonary vascular resistance during the first 30 s of ventilation; 2) a slower decline, which continues through the first 10-20 min or more of ventilation. Indomethacin has no effect on the first component. The second component is absent following indomethacin pretreatment. The effect of indomethacin treatment is more pronounced in immature fetuses (less than 90% gestation) than in mature fetuses. Prostaglandin synthase activity appears to be important in the pulmonary vasodilation caused by ventilation of the fetal lungs with air.

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Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.

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The effects of exogenous prostaglandin (PG) F2α, as well as PGF1α and the 15-keto metabolites of both prostaglandins, upon unventilated fetal, premature newborn, and mature newborn goat pulmonary and systemic circulations were examined by infusing the compounds into the pulmonary circulation. PGF2α is a powerful pressor agent in both pulmonary and systemic circulations of fetal and neonatal goats. Broncho–pulmonary constriction was also observed in ventilated animals at infusion rates in excess of the lung's ability to catabolize the prostaglandin. The pressor effects were not attenuated by alpha-adrenergic blockade. PGF1α is qualitatively similar, but quantitatively less, in its effect. The 15-keto metabolites did not alter pulmonary or systemic circulation even at very high doses. The PGF2α threshold dose for increasing pulmonary vascular resistance is lowest in the unventilated fetus, greatest in the premature newborn, and intermediate in the newborn older than 1 day of age. The lower sensitivity of the pulmonary circulation to the exogenous vasoconstrictor in the immediate postventilation period suggests the presence of endogenous dilator activity. Since the increase in pulmonary vascular resistance produced by indomethacin is greatest in the newly ventilated fetus, less in the older newborn, and negligible in the unventilated fetus, the substance(s) responsible for the endogenous dilator activity would appear to require prostaglandin fatty acid cyclooxygenase activity for production.