Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O₂ ^·) that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 ± 0.11 in unmanipulated control mice to 6.3 ± 0.16 in wild-type mice, but to only 5.60 ± 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wild-type). Hemorrhage-induced lipid peroxidation, as assessed by lung F₂ isoprostanes, was lower in the EC-SOD transgenic mice (3.4 ± 0.3 μ g/lung) compared with wild-type mice (1.9 ± 0.2 μ g/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK- κ B) activation (relative absorbance 1.1 ± 0.2 for EC-SOD transgenic versus 2.5 ± 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 ± 0.87 units/g for EC-SOD transgenic versus 11.3 ± 1.8 units/g for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse lung attenuates lung injury after hemorrhage.

Keywords: hemorrhage; extracellular superoxide dismutase; NF-κB; myeloperoxidase