DIASPIRIN CROSS-LINKED HEMOGLOBIN IMPROVES NEUROLOGICAL OUTCOME FOLLOWING REVERSIBLE BUT NOT IRREVERSIBLE CNS ISCHEMIA IN RABBITS

Background and Purpose Hemodilution using modified hemoglobin solution s may reduce ischemic central nervous system injury. Purified diaspiri n cross-linked hemoglobin (DCLHb) is a cell-free hemoglobin that is in tramolecularly cross-linked between the two alpha Subunits, resulting in enhanced oxygen offloading to tissues and increased half-life. In t he present experiments, we evaluated the ability of DCLHb to reduce ne urological damage in two rabbit stroke models. Methods In a reversible spinal cord ischemia model, ischemia of the caudal lumbar spinal cord was produced by temporary occlusion of the abdominal aorta. In an irr eversible model of cerebral ischemia, plastic microspheres (50 mu m) w ere injected into the internal carotid artery and lodged in the cerebr al microvasculature. DCLHb was administered 5 minutes after initiation of ischemia as either a 10-mL/kg infusion, 10-mL/kg exchange transfus ion, or a 20-mL/kg infusion. Control animals received human serum albu min that was oncotically matched to the DCLHb. Results In the spinal c ord model, DCLHb significantly increased the duration of ischemia requ ired to produce permanent paralysis from 27.33+/-8.71 minutes (mean+/- SD) in controls to 42.59+/-10.10 minutes in the 10-mL/kg exchange tran sfusion group and to 40.82+/-18.16 minutes in the 20-mL/kg infusion co ndition (P<.05). DCLHb did not significantly reduce neurological damag e in the microsphere embolization model. Conclusions These data sugges t that cross-linked hemoglobin reduces neurological damage after rever sible central nervous system ischemia and that this is not attributabl e to hemodilution or hypervolemia only.