Acute lung injury following reperfusion after ischemia in the hind limbs of rats.
In this study, we proposed that oxygen free radicals participate in the acute pulmonary injury that follows limb ischemia/reperfusion. Using an established model of hind limb ischemia, reproducible lung injury occurred after reperfusion. Lung microvascular permeability was measured with 125I-BSA and increased two-fold after 30 minutes of reperfusion. Pulmonary injury was blocked with DMSO, DMTU, allopurinol, indomethacin, and SOD plus catalase. The degree of pulmonary neutrophil sequestration as assessed by tissue myeloperoxidase activity was significantly diminished in animals pretreated with antioxidants. Pretreatment with indomethacin did not attenuate the neutrophil sequestration within the pulmonary parenchyma. These data suggest that increased lung microvascular permeability and neutrophil accumulation occur following hind limb ischemia/reperfusion. Therapeutic interventions with oxygen radical inhibitors blocked this process, while the prostaglandin inhibitor, indomethacin, only reduced lung permeability.
Punch
J
J
Department of Surgery, University of Michigan Medical School, Ann Arbor 48109-0340.
Rees
R
R
Cashmer
B
B
Oldham
K
K
Wilkins
E
E
Smith
D J
DJ
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability; D002374:Catalase / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005609:Free Radicals; D006614:Hindlimb / Q000098:blood supply*; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D005609:Free Radicals; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D013890:Thiourea; D007213:Indomethacin; D004121:Dimethyl Sulfoxide