ATTENUATION OF POSTISCHEMIC REPERFUSION INJURY IN STRIATED SKIN MUSCLE BY DIASPIRIN-CROSS-LINKED HB

Hemoglobin-based oxygen carriers have been suggested to enhance the fo rmation of oxygen free radicals, especially under conditions of ischem ia-reperfusion (I/R), in which activation and adhesion of leukocytes p lay a pivotal role for propagation of reperfusion injury. This study i nvestigates the effects of the hemoglobin-based oxygen carrier diaspir in-cross-linked hemoglobin (DCLHb) in an I/R model of hamster striated skin muscle. The dorsal skinfold chamber model in the awake Syrian go lden hamster was used for analysis of the microcirculation and local t issue Po, in striated skin muscle utilizing the technique of intravita l fluorescence microscopy and a multiwire platinum surface (Clark type ) electrode. Measurements were made before 4 h of pressure-induced isc hemia and at 0.5, 2, and 24 h of reperfusion. Animals were treated wit h 5 ml/kg body wt of either 10% DCLHb (n = 8), 6% Dextran 60 (Dx-60; 6 0 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 sign ificant decrease of leukocytes rolling along and sticking in postcapil lary venules, associated with a recovery of functional capillary densi ty and red blood cell velocity, was observed compared with saline-trea ted controls. In the early reperfusion period (0.5 h), DCLHb and Dx-60 efficiently restored local tissue Po,, whereas tissue Po, decreased f rom 18.3 +/- 1.9 to 15.3 +/- 5.3 mmHg in 0.9% NaCl-treated animals. El ectron microscopic analysis of the postischemic tissue at 24 h of repe rfusion revealed markedly reduced tissue damage in animals treated wit h DCLHb compared with Dx-60 or isotonic saline. These results indicate that DCLHb attenuates postischemic reperfusion injury of striated ski n muscle, presumably through alterations of leukocyte-endothelial cell interactions.