title: Ischemia-reperfusion injury.
abstract: Ischemia followed by reperfusion of the rat hind limb resulted in local evidence of injury, as reflected in increased vascular permeability and hemorrhage in skeletal muscle as well as distant organ injury, as reflected by increased vascular permeability and hemorrhage in lung. These changes were proportional to the duration of reperfusion and were associated with neutrophil accumulation in tissue, as quantitated by myeloperoxidase (MPO) content. There was corresponding evidence of complement depletion and increases in plasma IL-1 and IL-6. On the basis of interventional approaches, limb and lung vascular injury was neutrophil and complement dependent and was attenuated by treatment with antioxidants. Products of L-arginine were involved in the development of vascular injury since antagonists of L-arginine were protective. Based on the use of blocking antibodies, the cytokines TNF alpha and IL-1 were also involved in the development of tissue injury. Finally, both LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) beta 2 integrins were required as well as the endothelial adhesion molecules E-selectin and ICAM-1. Protective interventions were more protective that both local and remote organ injury following ischemia-reperfusion is in lung than in skeletal muscle. There were, in general, parallel effects when tissue protection was related to reduction in MPO content. These data suggest dependent on toxic oxygen and L-arginine products of neutrophils, the accumulation of which can be linked to cytokines (TNF alpha, IL-1), beta 2 integrins and endothelial adhesion molecules.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor.
authors.forename: A
authors.initials: A
authors.lastname: Seekamp
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D015427:Reperfusion Injury / Q000097:blood / Q000276:immunology / Q000503:physiopathology*
chemical_list: D015815:Cell Adhesion Molecules