Effects of hypoxia and reoxygenation on lung glutathione system

Reexpansion pulmonary edema (RPE) parallels reperfusion (reoxygenation) injuries in other organs in that hypoxic and hypoperfused lung tissue develops increased vascular permeability and neutrophil infiltration after reexpansion. This study investigated the lung cellular glutathione system during hypoxia (produced by lung collapse) and after reoxygenation (produced by reexpansion). Two separate groups of rabbits were studied to determine effects of lung hypoxia-reoxygenation on 1) lung glutathione peroxidase and reductase enzyme activities and 2) lung tissue, plasma, and alveolar lavage fluid total (reduced glutathione plus glutathione disulfide) and oxidized glutathione. Neither lung collapse for 3-7 days nor reexpansion for 2 h after 7 days of collapse affected glutathione peroxidase [controls, 0.36 +/- 0.04 (left), 0.38 +/- 0.03 U/mg DNA (right)] or reductase [controls, 0.12 +/- 0.01 (left), 0.14 +/- 0.01 U/mg DNA (right)] activities. The concentration of glutathione disulfide increased markedly in right alveolar lavage fluid, but not in plasma, after right lung reexpansion. Right lung total glutathione decreased significantly (-19%) after 7 days of collapse. After right lung reexpansion, both left (-65%) and right (-68%) lung total glutathione decreased significantly. The percent of total glutathione present in the oxidized form increased significantly in both left (to 15.5 +/- 4.0% of total) and right (to 18.7 +/- 6.3% of total) lungs after reexpansion of the right lung. These data indicate that lung tissue hypoxia, produced by unilateral lung collapse, was associated with a unilateral decrease in lung total glutathione content. Right lung reoxygenation, due to rapid reexpansion, caused a bilateral decrease in lung total glutathione content and an increase in right lung and alveolar lavage fluid glutathione disulfide concentration.