Effects of dextran and pentoxifylline on hemorrhagic shock-induced P-selectin expression

Background. Dextran and pentoxifylline have been shown to prevent leukocyte -endothelium adherence encountered after hemorrhagic shock, P-Selectin is t he first endothelial cell adhesion molecule to be upregulated after an isch emic insult. We investigated the effects of resuscitation with dextran 70 a nd administration of pentoifylline during resuscitation on hemorrhagic shoc k-induced P-selectin expression. Material and Methods. Hemorrhagic shock was induced in C57BL/6 mice by with drawing blood to reduce mean arterial blood pressure to 30 mm Hg for 45 min . Animals were resuscitated by infusing one of the following solutions teac h n:5): (1) Ringer's lactate, (2) 6% dextran 70, (3) Ringer's lactate plus 50 mg/kg pentoxifylline, (4) 5% human albumin. Afterward shed blood was inf used. In vivo P-selectin expression was determined using dual-radio-labeled monoclonal antibody technique in lung, heart, liver, kidney, mesentery, st omach, small bowel, and colon 5 h after resuscitation. Results. P-Selectin was significantly upregulated in all of the organs stud ied in the Ringer's lactate resuscitation group (P < 0.001), Resuscitation with dextran 70 and administration of pentoxifylline during resuscitation p revented P-selectin upregulation. Resuscitation with human albumin caused s ignificant attenuation but could not prevent P-selectin upregulation (p < 0 .01), Conclusion, Our study implies that the prevention of hemorrhagic shock-indu ced leukocyte-endothelium adherence by dextran 70 and pentoxifylline observ ed in other studies may be mediated by prevention of P-selectin expression by these agents. (C) 1999 Academic Press.