title: Cyanide-related changes in cerebral O2 delivery and metabolism in fluorocarbon-circulated rats.
abstract: Cyanide-induced cytotoxicity is primarily a result of inhibition of O2 uptake by the terminal enzyme of the mitochondrial respiratory chain, cytochrome-c oxidase (cytochrome aa3). The oxidase in the brain is highly vulnerable to cyanide cytotoxicity, but few studies have evaluated the effects of cyanide on cerebral oxygen metabolism. In the present study, we measured oxidation-reduction responses of cerebrocortical cytochrome aa3 to cyanide and related changes in cerebral blood flow (CBF) and O2 metabolism (CMRO2). Accurate measurement of cytochrome aa3 redox state in vivo by reflectance spectrophotometry was accomplished by using fluorocarbon-circulated rats to eliminate spectral interference from hemoglobin. The data indicate that constant intravenous infusions of cyanide caused rapid, progressive reduction responses by cerebrocortical cytochrome aa3 concomitant with increases in CBF of up to 200%. However, CMRO2 was maintained near normal until cerebral O2 delivery began to fall. These cerebral oxidative responses to cyanide may be explained either by redistribution of intracellular O2 supply to mitochondria respiring in an O2-dependent manner or by branching effects within brain mitochondria in vivo.
authors.affiliation: Department of Physiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: P A
authors.initials: PA
authors.lastname: Lee
authors.forename: A L
authors.initials: AL
authors.lastname: Sylvia
authors.forename: C A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003486:Cyanides / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003486:Cyanides; D005466:Fluorocarbons; D003576:Electron Transport Complex IV; D010100:Oxygen