title: S-nitrosylated pegylated hemoglobin reduces the size of cerebral infarction in rats.
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, 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.
authors.affiliation: Tokai University School of Medicine, Isehara, Kanagawa, Japan. akira@is.icc.u-tokai.ac.jp
authors.forename: Akira T
authors.initials: AT
authors.lastname: Kawaguchi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumoto
authors.forename: Mariko
authors.initials: M
authors.lastname: Yamano
authors.forename: Munetaka
authors.initials: M
authors.lastname: Haida
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D009460:Neurologic Examination; D015538:Nitrosation; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000737:chemistry; D013927:Thrombosis / Q000139:chemically induced
chemical_list: D006454:Hemoglobins; C109960:PEG-hemoglobin; D013778:Tetrazolium Salts; D011092:Polyethylene Glycols; C009591:triphenyltetrazolium