Role of leukocytes and tissue-derived oxidants in short-term skeletal muscle ischemia-reperfusion injury.
The relative contribution of xanthine oxidase (XO) and leukocytes to tissue injury after short-term ischemia is unknown. In this study, we subjected three groups of rat spinotrapezius muscles to 30-min ischemia and 1-h reperfusion: 1) ischemia-reperfusion (I/R) + 0.9% saline, 2) I/R + superoxide dismutase, and 3) I/R + oxypurinol. A fourth group served as nonischemic control. We quantified the increase in resistance (%DeltaR) caused by leukocyte-capillary plugging concurrently with myocyte uptake of propidium iodide (PI) [expressed as no. of PI spots per total volume of perfused tissue (N(PI)/V)] and performed assays to quantify XO activity, thiobarbituric acid-reactive substances (TBARS), and myeloperoxidase (MPO). Groups 2 and 3 exhibited significant decreases in N(PI)/V relative to group 1. MPO levels and TBARS were similar among all groups, and mean %DeltaR was significantly reduced in groups 2 and 3 relative to group 1. However, elevated XO was observed in groups 1 and 2 relative to group 3 and nonischemic controls. These data are consistent with the hypothesis that XO, rather than toxic species produced by plugging or venule-adherent leukocytes, is responsible for postischemic damage in this model.
Kadambi
A
A
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA.
Skalak
T C
TC
D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D002448:Cell Adhesion; D002465:Cell Movement; D005260:Female; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology; D016877:Oxidants / Q000502:physiology*; D010117:Oxypurinol / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012965:Sodium Chloride / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance; D014969:Xanthine Oxidase / Q000378:metabolism
D008054:Lipid Peroxides; D016877:Oxidants; D012965:Sodium Chloride; D009195:Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010117:Oxypurinol