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Direct measurement of nitroxide pharmacokinetics in isolated hearts situated in a low-frequency electron spin resonance spectrometer: implications for spin trapping and in vivo oxymetry

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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The pharmacokinetics of two nitroxides were investigated in isolated rat hearts situated in a low-frequency electron spin resonance spectrometer. The spin labels 2,2,3,3,5,5-hexamethyl-1-pyrrolidinyloxy and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy were chosen for their physiochemical analogy to the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and its corresponding spin-trapped adduct, 2-hydroxy-5,5-dimethyl-1-pyrrolidinyloxy (DMPO-OH). The bioreductive rates of the two nitroxides were measured during constant perfusion as well as during ischemia and are discussed in terms of a two-compartment pharmacokinetic model. These data provide information necessary to the design and application of spin traps to detect oxy radicals during reperfusion of ischemic tissue and suggest the feasibility of monitoring free-radical processes in intact, functioning mammalian tissues by using a low-frequency electron spin resonance spectrometer.

Research Organization:
Duke Univ. Medical Center, Durham, NC (USA)
OSTI ID:
6600559
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:20; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BODY
CARDIOVASCULAR SYSTEM
CHALCOGENIDES
ELECTRON SPIN RESONANCE
HEART
KINETICS
MAGNETIC RESONANCE
MAMMALS
MATHEMATICAL MODELS
MATHEMATICS
MEASURING METHODS
MUSCLES
MYOCARDIUM
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANS
OXIDES
OXYGEN COMPOUNDS
RATS
REACTION KINETICS
REGRESSION ANALYSIS
RESONANCE
RODENTS
STATISTICS
VERTEBRATES