S-nitrosylated pegylated hemoglobin reduces the size of cerebral infarction in rats.
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.
Kawaguchi
Akira T
AT
Tokai University School of Medicine, Isehara, Kanagawa, Japan. akira@is.icc.u-tokai.ac.jp
Nakai
Kunihiko
K
Fukumoto
Dai
D
Yamano
Mariko
M
Haida
Munetaka
M
Tsukada
Hideo
H
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
D006454:Hemoglobins; C109960:PEG-hemoglobin; D013778:Tetrazolium Salts; D011092:Polyethylene Glycols; C009591:triphenyltetrazolium