CELLULAR-RESPONSES TO SURGICAL TRAUMA, HEMORRHAGE, AND RESUSCITATION WITH DIASPIRIN CROSS-LINKED HEMOGLOBIN IN RATS

Background: Resuscitation with acellular oxygen carrier solutions offe rs the potential advantage of improved oxygen delivery compared with c rystalloid solutions, but the detailed consequences of improved resusc itation have not been fully evaluated, This study evaluated local and systemic cellular effects of trauma, hemorrhage, and resuscitation in a model of hemorrhage and surgical trauma. Methods: Rats with a 10 cm full-thickness incisional wound and a 15 mL/kg hemorrhage were either not resuscitated or resuscitated with blood or diaspirin cross-linked hemoglobin (DCLHb), Cellular proliferative responses were evaluated at 1.5, 6, 24, and 48 hours after wounding by labelling in vivo with 5-b romo-2'-deoxyuridine. Plasma levels of interleukin-6, tumor necrosis f actor-alpha; and interferon-gamma were measured by bioassay or enzyme- linked immunosorbent assay (ELISA), Bacterial translocation was measur ed by culturing liver homogenates. Results: Trauma inhibited keratinoc yte and hepatocyte proliferation at 1.5 and 6 hours, and stimulated su bsequent proliferation of keratinocytes and liver nonparenchymal cells , DCLHb stimulated wound keratinocyte proliferation, attenuated the in hibition of hepatocyte proliferation, eliminated bacterial translocati on to the liver, protected the intestine from ischemic damage, and ind uced a rapid increase of interleukin-6 during the early phase of injur y. Conclusions: Surgical trauma alone, or in combination with hemorrha ge, modulated cell proliferation both in the wound and in the remote o rgans of intestine and liver, DCLHb enhanced wound healing and cell pr oliferation as well as, or better than, freshly drawn blood, which may be beneficial for trauma care.