Prostaglandin I2 supports blood flow to hypoxic alveoli in anesthetized dogs.

In an animal model of unilateral alveolar hypoxia, inhibition of cyclooxygenase activity, estimates of immunoreactive 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and administration of prostaglandin I2 (PGI2) were used to evaluate the hypothesis that endogenous PGI2 opposes hypoxic pulmonary vasoconstriction, thereby producing redistribution of blood flow to hypoxic alveoli and reductions in systemic PO2. In anesthetized dogs, one lung was ventilated with 100% N2 and the other with 100% O2. Thermal dilution coupled with electromagnetic flow measurements permitted estimates of blood flow to each lung. Indomethacin or meclofenamate reduced flow to the N2-ventilated lungs (P less than 0.05) and increased systemic PO2 (P less than 0.05). Simultaneously, aortic concentrations of immunoreactive 6-keto-PGF1 alpha decreased 63 +/- 8% (P less than 0.001). Following cyclooxygenase inhibition, incremental doses of PGI2 (0.01, 0.025, and 0.10 micrograms X kg-1 X min-1) increased flow to the N2-ventilated lungs and reduced systemic PO2 (P less than 0.001) without affecting mixed venous PO2. These results suggest that systemic PO2 was reduced because of increased venous admixture. We conclude that PGI2 attenuates hypoxic vasoconstriction which allows flow to be maintained to hypoxic alveoli, resulting in reduced systemic PO2.