DESIGN: Prospective randomized, controlled experimental study.
SETTING: University center.
MEASUREMENTS AND MAIN RESULTS: In rat primary cortical neuron cultures, control bovine
hemoglobin was neurotoxic (
lactate dehydrogenase release; 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium
bromide assay) at concentrations from 12.5 to 0.625 μM, whereas
polyethylene glycol-conjugated
hemoglobin showed intermediate toxicity. PNPH was not neurotoxic (p<.05 vs. bovine
hemoglobin and
polyethylene glycol hemoglobin; all concentrations). PNPH conferred neuroprotection in in vitro neuronal injury (
glutamate/
glycine exposure and neuronal stretch), as assessed via
lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl-]-2,5-diphenyltetrazolium
bromide (all p<.05 vs. control). C57BL6 mice received controlled cortical impact followed by hemorrhagic
hypotension (2 mL/100 g, mean arterial blood pressure ∼35-40 mm Hg) for 90 min. Mice were resuscitated (mean arterial blood pressure>50 mm Hg for 30 min) with
lactated Ringer's, Hextend, or PNPH, and then shed blood was reinfused. Mean arterial blood pressures,
resuscitation volumes, blood gasses,
glucose, and
lactate were recorded. Brain sections at 7 days were examined via
hematoxylin and
eosin and
Fluoro-Jade C (identifying dying neurons) staining in CA1 and CA3 hippocampus.
Resuscitation with PNPH or Hextend required less volume than
lactated Ringer's (both p<.05). PNPH but not Hextend improved mean arterial blood pressure vs.
lactated Ringer's (p<.05). Mice resuscitated with PNPH had fewer
Fluoro-Jade C positive neurons in CA1 vs. Hextend and
lactated Ringer's, and CA3 vs. Hextend (p<.05).
CONCLUSIONS: