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.
Rosen
G M
GM
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Halpern
H J
HJ
Brunsting
L A
LA
Spencer
D P
DP
Strauss
K E
KE
Bowman
M K
MK
Wechsler
A S
AS
D000818:Animals; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D006207:Half-Life; D008433:Mathematics; D009206:Myocardium / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013113:Spin Labels
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; C017245:5,5-dimethyl-1-pyrroline-1-oxide