Heparin-released superoxide dismutase inhibits postischemic leukocyte adhesion to venular endothelium.

Details

Serval ID
serval:BIB_6217B63C5C78
Type
Article: article from journal or magazin.
Collection
Publications
Title
Heparin-released superoxide dismutase inhibits postischemic leukocyte adhesion to venular endothelium.
Journal
American Journal of Physiology
Author(s)
Becker M., Menger M.D., Lehr H.A.
ISSN
0363-6135
0002-9513 (Print)
ISSN-L
0002-9513
Publication state
Published
Issued date
1994
Volume
267
Number
3 Pt 2
Pages
H925-H930
Language
english
Abstract
Superoxide radicals formed during reperfusion of ischemic tissues have been identified as a key mediator in the microvascular manifestations of postischemic tissue damage. This understanding is based on studies in laboratory animals in which high doses of superoxide dismutase (SOD; 2.0-25.0 mg/kg body wt iv) were found to inhibit postischemic leukocyte adhesion and the leakage of fluid and macromolecules. Using a dorsal skinfold chamber model in hamsters, we demonstrate now that protection from reperfusion-induced leukocyte adhesion to venular endothelium after 4 h of ischemia to striated muscle can be attained by pretreatment of the animals with a significantly lower dose of exogenous CuZn-SOD (0.25 mg/kg body wt) or with heparin (2,000 IU/kg body wt), which induces a comparable increase in SOD plasma activity through the release of endogenous extracellular SOD from endothelial cell binding sites. This protective effect was maintained until 24 h after reperfusion. In contrast, CuZn-SOD or heparin failed to attenuate the postischemic shutdown of nutritional capillary perfusion, a phenomenon that is due to ischemia-induced endothelial cell swelling, rather than due to reperfusion-associated events, and hence is not susceptible to strategies directed against oxygen radicals generated during the reperfusion phase. The results of this study 1) imply that postischemic leukocyte/endothelium interaction can be attenuated by a low and clinically more relevant dose of SOD, and 2) caveat the administration of heparin in laboratory animals (i.e., to keep catheters patent) in studies of experimental ischemia/reperfusion injury or other oxygen radical-dependent pathomechanisms.
Keywords
Animals, Capillaries/drug effects, Cell Adhesion/drug effects, Cricetinae, Dose-Response Relationship, Drug, Endothelium, Vascular/physiology, Heparin/pharmacology, Ischemia/pathology, Ischemia/physiopathology, Leukocytes/physiology, Mesocricetus, Muscles/blood supply, Reperfusion, Superoxide Dismutase/administration & dosage, Superoxide Dismutase/pharmacology, Venules/physiology
Pubmed
Create date
25/11/2011 19:15
Last modification date
20/08/2019 14:19
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