title: Rat maze performance after resuscitation with cross-linked hemoglobin solution.
abstract: Unmodified stroma-free hemoglobin has been found to produce neurotoxicity and behavioral impairment in rats. In contrast, a recent assessment of a modified (diaspirin alpha-alpha cross-linked) hemoglobin (HbXL) solution found normal memory, learning, and brain histology after infusion of a clinically relevant dose of a 14% HbXL solution. The current study examined this potential resuscitation fluid for evidence of neurobehavioral toxicity under clinical conditions. Rats were trained to complete a water alley maze, had 50% of their total blood volume (30 ml/kg) withdrawn, were resuscitated with 14% HbXL solution (45 ml/kg), Ringer's lactate (60 ml/kg), or autologous shed blood, and were subsequently retested in the water maze. Rats resuscitated with HbXL or autologous shed blood survived resuscitation, while 20% of those resuscitated with Ringer's lactate died during treatment. No significant performance degradation was observed in the HbXL rats following resuscitation, and no brain pathology was observed at necropsy 10 days after treatment. Ischemic brain lesions were observed in three (25%) of the surviving rats resuscitated with Ringer's lactate solution. Renal tubule regeneration indicative of an earlier insult was observed in animals from all three groups. A significant correlation between the total pathology in the five organs examined and maze errors was observed (p less than 0.001). The survival, maze performance, and histology results suggest that resuscitation with 14% HbXL solution does not cause neurotoxicity, as assessed in this lethal hemorrhage model.
authors.affiliation: Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C.
authors.forename: R J
authors.initials: RJ
authors.lastname: Przybelski
authors.forename: G J
authors.initials: GJ
authors.lastname: Kant
authors.forename: M J
authors.initials: MJ
authors.lastname: Bounds
authors.forename: M V
authors.initials: MV
authors.lastname: Slayter
authors.forename: R M
authors.initials: RM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001804:Blood Transfusion, Autologous; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006454:Hemoglobins / Q000008:administration & dosage* / Q000032:analysis; D007773:Lactates / Q000008:administration & dosage; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051381:Rats; D012151:Resuscitation; D012996:Solutions
chemical_list: D006454:Hemoglobins; D007773:Lactates; D012996:Solutions