High-frequency ventilation attenuation of hypoxic pulmonary vasoconstriction. The role of prostacyclin

In order to determine the effects of high-frequency ventilation on the pulmonary vascular response to hypoxia, we assessed pulmonary vascular resistance at 2 levels of inspired oxygen tension (PI(O₂)), 200 and 30 mmHg, during conventional and high-frequency ventilation in the isolated, blood-perfused lungs of 10 sheep, 5 treated with indomethacin (40 μg/ml of perfusate) and 5 untreated. Resistance was assessed by measuring pulmonary artery pressure-flow curves generated over a wide range of flows (20 to 140 ml·min^-1·kg body wt^-1). Conventional ventilation was provided by an animal ventilator at a rate of 10 min^-1 and a tidal volume of 10 ml·kg body wt^-1. High-frequency ventilation was provided by a flow interrupter at a rate of 1,200 min^-1 and a tidal volume less than 1.5 ml·kg body wt^-1. In the 5 untreated lungs, the normoxic pressure-flow curve was unaltered by high-frequency ventilation, but the hypoxic pulmonary vasoconstrictor response was significantly attenuated. Furthermore, the net rate of change of 6-keto-prostaglandin F(1α) concentration in the perfusate during hypoxia was significantly greater with high-frequency ventilation (65.4 ± 8.9 pg·ml_-1·min^-1) than with conventional ventilation (2.8 ± 18.7 pg·ml^-1·min^-1). In the 5 indomethacin-treated lungs, production of 6-keto-prostaglandin F(1α) was markedly depressed, and the attenuation of the hypoxic vasoconstrictor response by high-frequency ventilation was abolished. These results demonstrate that in isolated sheep lungs, high-frequency ventilation attenuated the pulmonary vascular response to hypoxia and suggest that this attenuation could be due to enhanced prostacyclin release by the lungs.