RESIDENT RESEARCH AWARD - A NOVEL NONANTICOAGULANT HEPARIN IMPROVES SPLENOCYTE AND PERITONEAL MACROPHAGE IMMUNE FUNCTION AFTER TRAUMA-HEMORRHAGE AND RESUSCITATION

Recent studies have shown that heparinization of animals prior to or e ven after hemorrhagic shock improves tissue perfusion and organ functi on. However, the anticoagulant properties of conventional heparin prec lude its clinical use in trauma care. The aim of our study, therefore, was to determine whether chemically modified heparin, i.e., a novel n onanticoagulant heparin (GM1892), which does not have significant anti coagulant activity (similar to 2% of the anticoagulant activity of con ventional heparin), produces any beneficial effects on splenocyte and macrophage immune function following trauma-hemorrhage and resuscitati on. To determine this, following the induction of tissue trauma (i.e., a midline laparotomy), mice were bled to and maintained at a mean art erial pressure of 35 mm Hg for 1 hr. The animals then received GM1892 (7 mg/kg body wt), conventional heparin (7 mg/kg body wt), or normal s aline prior to resuscitation with three times the volume of shed blood with Ringer's lactate. Two hours after resuscitation the animals were sacrificed, splenocytes were isolated, and splenic, as well as perito neal macrophage, cultures were established. The ability of the splenoc ytes to release IL-2 and IL-3 in response to mitogen was markedly impr oved in hemorrhaged animals which were treated with GM1892 or conventi onal heparin compared to saline-treated mice. Furthermore, the capacit y of splenic and peritoneal macrophages to release IL-6 was restored i n the hemorrhaged animals that received GM1892 or conventional heparin . Since GM1892 does not have any significant anticoagulant properties and since it restores or significantly improves splenocyte and periton eal macrophage immune function, this agent may be a useful adjunct in the treatment of trauma-hemorrhagic shock-induced immunodepression, ev en in the absence of blood resuscitation. (C) 1995 Academic Press, Inc .