Effects of oxaceprol on the microcirculation in ischemia/reperfusion injury.
Oxaceprol, an established drug for treatment of degenerative joint disease, has recently been shown in vitro to reduce leukocyte adhesion to cultured endothelial cells and leukocyte extravasation in vivo in an arthritis animal model. The aim of this study was to examine the effects of Oxaceprol on the microcirculation of striated skin muscle. In the dorsal skinfold chamber of the awake Syrian golden hamster I/R injury was induced by applying a 4-hour complete pressure ischemia. Prior to the ischemia, after 30 minutes, 2 hours and 24 hours of reperfusion the following parameters were assessed in a blinded study: macromolecular leakage, leukocyte rolling fraction, adherent leukocytes, and functional capillary density (FCD). Rhodamine 6G to stain leukocytes in-vivo and FITC Dextran (MW 150,000) was used as a plasma marker. 15 minutes prior to reperfusion the animals received either an i.v. bolus infusion of Oxaceprol (50mg/kg) or an equivalent volume of saline, which was followed by a 45-minute continuous infusion at the same dose. At the conclusion of the experiment samples were collected from the chamber tissue for histological quantification of leukocyte extravasation using an esterase stain. Oxaceprol treatment resulted in a significant decrease of postischemic leukocyte adherence after 0.5 h and 2h of reperfusion. The histological sections revealed a significant reduction in the number of extravasated leukocytes. There was a reduction of macromolecular leakage and treatment also resulted in a preservation of tissue perfusion, as was indicated by a significant increase in FCD in the treatment group compared to the ischemia group. In summary, Oxaceprol was able to protect the tissue from ischemia/reperfusion injury.
Harris
A
A
Institute for Surgical Research, Klinikum Grosshadern, Marchioninistr. 15, Munich, D-81366, Germany.
Schropp
A
A
Messmer
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D006224:Cricetinae; D003911:Dextrans; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D006909:Hydroxyproline / Q000031:analogs & derivatives* / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology; D012867:Skin / Q000098:blood supply* / Q000166:cytology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; C012393:oxaceprol; D006909:Hydroxyproline