Effects of polyethylene glycol-linked superoxide dismutase and catalase during in vivo lung ischemia and reperfusion

We have previously demonstrated that reperfusion of a rabbit lung following 24 hours of in vivo pulmonary artery occlusion results in bilateral lung edema and lung inflammation and in systemic leukopenia. We tested whether this in vivo ischemia/reperfusion lung injury in the rabbit could be prevented by the administration of superoxide dismutase (SOD) and catalase (CAT). Polyethylene glycol-linked SOD (PEG-SOD) and CAT (PEG-CAT) were administered to five rabbits, PEG-SOD alone to four rabbits, and neither to nine untreated control rabbits, and the left pulmonary artery was then occluded with a microvascular clamp. Enzyme activity measured at the time of reperfusion 24 hours later demonstrated plasma CAT activity of 1,127 ± 601 U/mL for SOD/CAT-treated rabbits versus 193 ± 25 U / mL for untreated rabbits (P < .05) and SOD activity of 97 ± 25 U/mLfor SOD-treated rabbits versus no measurable activity in untreated rabbits. Following 4 hours of reperfusion, wet to dry ratios were 6.15 ± 0.27 for the reperfused left lungs and 5.55 ± 0.20 for the right lungs. Analysis of variance demonstrated a significant effect of reperfusion on left versus right wet to dry ratios (P < .05) but no effect of enzyme treatment. Lung sections scored by a blinded observer for histologic evidence of lung injury similarly showed a left-to-right difference but no difference between treated and untreated animals in degree of injury to the reperfused left lung. However, the contralateral lung was relatively less injured in treated rabbits. The two groups also differed in that an immediate leukopenia developed following reperfusion in the untreated and PEG-SOD-treated rabbits but not in the rabbits treated with both PEG-SOD and PEG-CAT. We conclude that SOD and CAT prevent the systemic leukopenia that accompanies pulmonary artery reperfusion, but do not prevent the injury to the reperfused lung. The sparing effect on the contralateral lung suggests that the mechanism of injury for that lung differs from the mechanism of injury to the occluded lung.