The Role of Oxygen-Derived Free Radicals in Ischemia-Induced Increases in Canine Skeletal Muscle Vascular Permeability

• Published in: Circulation research 1985-10, Vol.57 (4), p.599-609
• Main Authors: Korthuis, Ronald J, Granger, Neil D, Townsley, Mary I, Taylor, Aubrey E
• Format: Article
• Language: English
• Subjects: Allopurinol - pharmacology; Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Blood Pressure; Capillaries - physiology; Capillary Permeability; Cardiology. Vascular system; Catalase - pharmacology; Cimetidine - pharmacology; Dimethyl Sulfoxide - pharmacology; Diphenhydramine - pharmacology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dogs; Female; Free Radicals; Ischemia - physiopathology; Male; Medical sciences; Muscles - blood supply; Osmotic Pressure; Oxygen; Superoxide Dismutase - pharmacology; Vascular Resistance - drug effects
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.57.4.599

Previous studies indicate that vascular permeability is increased in skeletal muscle subjected to 4 hours of inflow occlusion. However, the mechanism(s) underlying the increase in permeability are unknown. The aim of this study was to assess the role of oxygen-derived free radicals and histamine as putative mediators of the increased permeability in skeletal muscle subjected to 4 hours of inflow occlusion. The osmotic reflection coefficient for total plasma proteins and isogravimetric capillary pressure were estimated in canine gracilis muscle for the following conditionscontrol, ischemia, and ischemia plus pretreatment with allopurinol (a xanthine oxidase inhibitor), catalase (a peroxidase that reduces hydrogen peroxide to water and molecular oxygen), superoxide dismutase (a superoxide anion scavenger), dimethyl sulfoxide (a hydroxyl radical scavenger), diphenhydramine (a histamine H1-receptor blocker), or cimetidine (a histamine H2-receptor blocker). Ischemia, followed by reperfusion, significantly reduced the reflection coefficient from 0.94 ± 0.02 to 0.64 ± 0.02 and isogravimetric capillary pressure from 13.8 ± 1.0 mm Hg to 6.9 ± 0.4 mmHg, indicating a dramatic increase in microvascular permeability. Prior treatment with diphenhydramine or cimetidine did not significantly alter the permeability increase induced by ischemia. However, pretreatment with allopurinol, catalase, superoxide dismutase, or dimethylsulfoxide did significantly attenuate the increase in vascular permeability. The results of this study indicate that oxygen radicals are primarily responsible for the increased vascular permeability produced by ischemia-reperfusion, that the hydroxyl radical may represent the primary damaging radical, and that xanthine oxidase may represent the primary source of oxygen-derived free radicals in ischemic skeletal muscle. (Circ Res 57599-609, 1985)