Mechanisms of stimulation of pulmonary prostacyclin synthesis at birth

In order to investigate the mechanism behind ventilation-induced pulmonary prostacyclin production at birth, chloralose anesthetized, exteriorized, fetal lambs were ventilated with a gas mixture that did not change blood gases (fetal gas) and unventilated fetal lungs were perfused with blood containing increased O₂ and decreased CO₂. Ventilation with fetal gas (3%O₂, 5%CO₂) increased net pulmonary prostacyclin (as 6-keto-PGF_1α production from -5.1 ± 4.4 to +12.6 ± 7.6 ng/kg·min. When ventilation was stopped, net pulmonary prostacyclin production returned to nondetectable levels. Ventilation with gas mixtures which increased pulmonary venous P_O2 and decreased P_O2 also stimulated pulmonary prostacyclin production, but did not have greater effects than did ventilation with fetal gas. In order to determine if increasing P_O2 or decreasing P_CO2 could stimulate pulmonary prostacyclin production independently from ventilation, unventilated fetal lamb lungs were perfused with blood that had P_O2 and P_CO2 similar to fetal blood, blood with elevated O₂, and blood that had P_O2 and P_CO2 values similar to arterial blood of newborn animals. Neither increased O₂ nor decreased CO₂ in the blood perfusing the lungs stimulated pulmonary prostacyclin synthesis. We conclude that the mechanism responsible for the stimulation of pulmonary prostacyclin with the onset of ventilation at birth is tissue stress during establishment of gaseous ventilation and rhythmic ventilation.