INHIBITION OF WHITE BLOOD-CELL ADHESION AT REPERFUSION DECREASES TISSUE-DAMAGE IN POSTISCHEMIC STRIATED-MUSCLE

Purpose: To determine the impact of white blood cell (WBC)-endothelium adhesion on tissue damage in the setting of ischemia-reperfusion inju ry in striated muscle. Methods: The cremaster muscle of four groups of anesthetized Sprague-Dawley rats was subjected to 4 hours of global, warm (37 degrees C) ischemia and 2 hours of reperfusion. At reperfusio n two groups of animals received intravenous injections of monoclonal antibodies directed against either CD11b/CD18 (1B6) or ICAM-1 (1A29). The remaining two groups of animals received saline injections (NoR(x) ) or nonreactive IgG(1). In vivo light microscopic techniques were use d to determine WBC adherence (number of WBCs per 100 mu m postcapillar y venules) at different intervals of reperfusion. Muscle viability was assessed with computer-assisted image analysis by measuring the optic al intensity of transilluminated muscles after incubation with nitrobl ue tetrazolium. Results: Our results (mean +/- SEM) demonstrate a sign ificant increase in the number of adherent WBCs relative to baseline ( 8.0 +/- 0.5) after 4 hours of global ischemia in animals receiving NoR (x) or IgG,. The significant increase occurred at 30 minutes of reperf usion (17.6 +/- 0.6 and 17.4 +/- 0.4 for NoR(x), or IgG(1), respective ly) and was sustained for the duration of the experiment. This Increas e in adherence was attenuated by 1B6 and 1A29 (12.2 +/- 2.2 and 12.4 /- 0.8, respectively; p < 0.05 compared with NoR(x) and IgG(1)). The d ecrease in WBC adhesion was associated with a decrease in reperfusion injury to the muscle, as indicated by lower optical intensity values f or the 1B6 and 1A29 groups (123 +/- 3 and 129 +/- 2) compared with the NoR(x), and IgG(1) groups (151 +/- 2 and 158 +/- 4). Conclusions: Our data support an important role for WBCs in the pathogenesis of ischem ia-reperfusion injury. Interfering with the WBC-endothelium interactio ns by using monoclonal antibodies directed against WBCs and endothelia l cell adhesion molecules may help to limit ischemia-reperfusion injur y.