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
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), Vol. 85:20
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
NITROGEN OXIDES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
ELECTRON SPIN RESONANCE
MATHEMATICAL MODELS
MEASURING METHODS
MYOCARDIUM
RATS
REGRESSION ANALYSIS
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
CHALCOGENIDES
HEART
KINETICS
MAGNETIC RESONANCE
MAMMALS
MATHEMATICS
MUSCLES
NITROGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
REACTION KINETICS
RESONANCE
RODENTS
STATISTICS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology