S-nitrosylated pegylated hemoglobin reduces the size of cerebral infarction in rats

Akira T. Kawaguchi, Kunihiko Nakai, Dai Fukumoto, Mariko Yamano, Munetaka Haida, Hideo Tsukada

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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, P50 = 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.

Original languageEnglish
Pages (from-to)183-188
Number of pages6
JournalArtificial Organs
Volume33
Issue number2
DOIs
Publication statusPublished - 2009 Feb

Keywords

  • Brain ischemia
  • Cerebral infarction
  • Microcirculation
  • Nitric oxide
  • Nitric oxide donor
  • Nitric oxide scavenger
  • Oxygen delivery
  • Reperfusion
  • S-nitrosylated hemoglobin

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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