Microvascular ischemia-reperfusion injury in striated muscle: significance of "reflow paradox".
Ischemia-reperfusion (I/R)-induced microvascular injury is characterized by capillary "no-reflow" and reflow-associated events, termed "reflow paradox," including leukocyte-endothelium interaction and increase in microvascular permeability. The major objectives of this study were 1) to elucidate the significance of reflow paradox after 4 h of tourniquet-induced ischemia in striated muscle and 2) to determine the role of reactive oxygen metabolites in the pathogenesis of reflow paradox-dependent microcirculatory alterations. By use of in vivo fluorescence microscopy in a striated muscle preparation of hamsters, leukocyte-endothelium interaction in postcapillary venules and macromolecular extravasation from capillaries and venules were quantified before ischemia and after 30 min, 2 h, and 24 h of reperfusion. I/R elicited marked enhancement (P < 0.01) of leukocyte rolling during initial reperfusion and a 20-fold increase of leukocyte adherence (P < 0.01) lasting for the entire postischemic reperfusion period (n = 7). These phenomena were accompanied by significant leakage (P < 0.01) of macromolecules from capillaries and in particular from postcapillary venules (n = 9). Both superoxide dismutase (SOD, 20 mg/kg body wt, n = 7) and allopurinol (50 mg/kg body wt, n = 7) were effective in attenuating I/R-induced leukocyte rolling and adherence. In addition, microvascular leakage was significantly reduced by allopurinol (n = 9) and completely abolished by SOD (n = 9) (P < 0.01). These results support the concept that reactive oxygen metabolites contribute to I/R-induced reflow paradox, resulting in leukocyte accumulation, adherence, and increase in microvascular permeability.
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D006224:Cricetinae; D003911:Dextrans; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D009132:Muscles / Q000098:blood supply*; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D000493:Allopurinol; D013482:Superoxide Dismutase; D016650:Fluorescein-5-isothiocyanate