Attenuation of postischemic reperfusion injury in striated skin muscle by diaspirin-cross-linked Hb.
Hemoglobin-based oxygen carriers have been suggested to enhance the formation of oxygen free radicals, especially under conditions of ischemia-reperfusion (I/R), in which activation and adhesion of leukocytes play a pivotal role for propagation of reperfusion injury. This study investigates the effects of the hemoglobin-based oxygen carrier diaspirin-cross-linked hemoglobin (DCLHb) in an I/R model of hamster striated skin muscle. The dorsal skinfold chamber model in the awake Syrian golden hamster was used for analysis of the microcirculation and local tissue PO2 in striated skin muscle utilizing the technique of intravital fluorescence microscopy and a multiwire platinum surface (Clark type) electrode. Measurements were made before 4 h of pressure-induced ischemia and at 0.5, 2, and 24 h of reperfusion. Animals were treated with 5 ml/kg body wt of either 10% DCLHb (n = 8), 6% Dextran 60 (Dx-60; 60 kDa, n = 8), or 0.9% NaCl (n = 7), which was given intravenously 15 min before reperfusion. In animals treated with DCLHb or Dx-60, a significant decrease of leukocytes rolling along and sticking in postcapillary venules, associated with a recovery of functional capillary density and red blood cell velocity, was observed compared with saline-treated controls. In the early reperfusion period (0.5 h), DCLHb and Dx-60 efficiently restored local tissue PO2, whereas tissue PO2 decreased from 18.3 +/- 1.9 to 15.3 +/- 5.3 mmHg in 0.9% NaCl-treated animals. Electron microscopic analysis of the postischemic tissue at 24 h of reperfusion revealed markedly reduced tissue damage in animals treated with DCLHb compared with Dx-60 or isotonic saline. These results indicate that DCLHb attenuates postischemic reperfusion injury of striated skin muscle, presumably through alterations of leukocyte-endothelial cell interactions.
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, 81377 Munich, Germany.
S
S
Pickelmann
D
D
Nolte
R
R
Leiderer
E
E
Schütze
K
K
Messmer
D000818:Animals; D001160:Arterioles / Q000502:physiology / Q000503:physiopathology / Q000648:ultrastructure; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D001802:Blood Substitutes / Q000627:therapeutic use*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology / Q000648:ultrastructure; D006339:Heart Rate; D006454:Hemoglobins / Q000627:therapeutic use*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000098:blood supply*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D014699:Venules / Q000502:physiology / Q000503:physiopathology / Q000648:ultrastructure
D001802:Blood Substitutes; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin