LEUKOCYTE-ENDOTHELIAL CELL-INTERACTIONS IN THE LIVER AFTER HEMORRHAGIC-SHOCK IN THE RAT

Leukocyte-endothelial cell interactions in rat livers were investigated using intravital fluorescence microscopy following hemorrhagic shock (MAP at 40 mm Hg for 60 min) and resuscitation. Thirty minutes after resuscitation, when MAP was higher than 1 00 mm Hg, sinusoidal perfusion was only slightly reduced (> 90% of controls). Firm adhesion of leukocytes increased to 370 +/- 54 leukocytes/mm2 after shock and resuscitation compared to control animals (48 +/- 8/mm2; mean +/- SEM; P < .01). Leukocyte-endothelium adhesion was highest in the portal areas and lowest in midzonal and pericentral regions (relationship: 2.0 : 1.1 : 1.0). Pretreatment with dexamethasone (5 mg/kg bw) resulted in a dramatic rise of adherent leukocytes following hemorrhagic shock (920 +/- 62/mm2; p < .001). Pretreatment with ibuprofen (15 mg/kg bw) resulted in a similar increase of adherent leukocytes after hemorrhagic shock (750 +/- 60/mm2; P < .001), while pretreatment with MK 886(10 mg/kg), inhibitor of lipoxygenase pathway, reduced leukocyte adhesion slightly (270 +/- 38/mm2). The results reveal that leukotrienes, e.g., released by activated macrophages, are involved in the regulation of leukocyte adhesion in liver sinusoids following hemorrhagic shock and resuscitation. The negative effect of dexamethasone and ibuprofen on hepatic leukocyte adhesion, however, has to be considered for therapeutic use.