Mechanisms of postischemic vascular dysfunction in skeletal muscle: implications for therapeutic intervention.
In 1981, it was first proposed that xanthine oxidase-derived reactive oxygen metabolites contribute to the microvascular and parenchymal cell damage which occurs when ischemic tissues are reperfused. Figure 1 summarizes a scheme that has been proposed to explain the interaction of xanthine oxidase-derived oxidants, neutrophil infiltration, and the microvascular dysfunction which occurs in postischemic tissue. According to this proposal, xanthine oxidase-derived oxidants, produced at the time of reperfusion, initiate the formation and release of proinflammatory agents, which subsequently attract and activate neutrophils. The activated granulocytes adhere to vascular endothelium, extravasate, and release cytotoxic oxidants and/or non-oxidative toxins (e.g. proteases) which contribute to tissue destruction. The objective of this review is to summarize the supportive evidence for this scheme in postischemic skeletal muscle and to identify the components of the mechanism that may be amenable to pharmacologic intervention.
Carden
D L
DL
Department of Physiology, LSU Medical Center, School of Medicine, Shreveport, LA 71130.
Korthuis
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005609:Free Radicals; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply*; D009504:Neutrophils / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005609:Free Radicals; D014969:Xanthine Oxidase; D010100:Oxygen