F₂-isoprostane generation in isolated ferret lungs after oxidant injury or ventilated ischemia

Pulmonary edema develops when pulmonary blood flow is interrupted, then restored. Because the lung is not always hypoxic when ischemic, mechanisms of pulmonary ischemia-reperfusion injury are likely to differ from systemic organs, where reactive oxygen species generated during reperfusion mediate organ dysfunction. We previously showed that pulmonary vascular permeability of isolated ferret lungs increased prior to reperfusion, if ventilation was maintained while blood flow was impaired. To determine whether reactive oxygen metabolites generated during ischemia mediated ischemic injury, we measured tissue levels of F₂-isoprostanes as an index of lipid peroxidation, 30 min after administration of glucose (5 mM)-glucose oxidase (GOX, 0.1 U/ml), or after short (45 min) or long (180 min) ventilated ischemia, in isolated ferret lungs. Osmotic reflection coefficient for albumin (σ(alb)), an estimate of vascular protein permeability, was measured in the same lungs. Tissue F₂-isoprostanes increased 375% after exposure to glucose-GOX in association with a 42% decrease in σ(alb), and administration of catalase (CAT, 100,000 U) and superoxide dismutase (SOD, 25,000 U) completely attenuated this lipid peroxidation. In contrast, tissue F₂-isoprostanes increased only 60% following 45 min of ischemia, then did not increase additionally. σ(alb) was not altered by 45 min of ischemia, but decreased 72% following 180 min of ischemia. CAT + SOD did not alter F₂-isoprostane formation during ischemia, but partially attenuated vascular injury. These results suggest that tissue levels of F₂-isoprostanes reflect lung lipid peroxidation, but that F₂-isoprostane generation does not directly increase vascular permeability following ventilated pulmonary ischemia.