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S ‐Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in Rats
Author(s) -
Kawaguchi Akira T.,
Nakai Kunihiko,
Fukumoto Dai,
Yamano Mariko,
Haida Munetaka,
Tsukada Hideo
Publication year - 2009
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.2008.00705.x
Subject(s) - hemoglobin , peg ratio , cerebral infarction , infarction , extravasation , medicine , anesthesia , ischemia , pharmacology , chemistry , pathology , myocardial infarction , finance , economics
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.