Cell-free
hemoglobin-based
oxygen carriers have well-documented safety and efficacy problems such as
nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S-nitrosylated pegylated
hemoglobin (SNO-
PEG-Hb, P(50) = 12 mm Hg) and tested it in a
brain ischemia and reperfusion model. Neurological function and extent of
cerebral infarction was determined 24 h after photochemically induced
thrombosis of the middle cerebral artery in the rat.
Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by
triphenyltetrazolium chloride staining in rats receiving various doses of SNO-
PEG-Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated
hemoglobin without S-nitrosylation (
PEG-Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO-
PEG-Hb but not
PEG-Hb to be effective in reducing the size of cortical
infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO-
PEG-Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical
infarction, however, without functional improvement.