Electron paramagnetic resonance imaging of rat heart with nitroxide and polynitroxyl-albumin.

Abstract:

:Electron paramagnetic resonance (EPR) imaging utilizing stable nitroxyl radicals is a promising technique for measuring free radical distribution, metabolism, and tissue oxygenation in organs and tissues [Kuppusamy, P., Chzhan, M., Vij, K., Shteynbuk, M., Lefer, D. J., Giannella, E., & Zweier, J. L. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 3388-3392]. However, the technique has been limited by the rapid reduction of nitroxide in vivo to its hydroxylamine derivative, a diamagnetic, EPR-inactive species. In this report a novel, polynitroxylated derivative of human serum albumin is shown to be capable of reoxidizing the hydroxylamine back to nitroxide in vivo. Polynitroxyl-albumin (PNA) is shown to be effective in maintaining the signal intensity of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL or TPL) in the ischemic isolated rat heart, allowing the acquisition of high-resolution three-dimensional (3D) EPR images of the heart throughout a prolonged 2.5 h period of global cardiac ischemia. In serial transverse sections of the 3D image, TPL intensity maps of the heart showed cardiac structure with submillimeter resolution. TPL intensities in coronary arteries and myocardium showed that nitroxide concentration decreases with increasing distance from large blood vessels. These results demonstrate that EPR imaging in vivo is possible using nitroxides in conjunction with PNA. In addition to its utility in the emerging technology of EPR imaging, the greatly prolonged half-life of TPL observed in the presence of PNA may facilitate the therapeutic application of nitroxides in a variety of disease processes.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Kuppusamy P,Wang P,Zweier JL,Krishna MC,Mitchell JB,Ma L,Trimble CE,Hsia CJ

doi

10.1021/bi952857s

subject

Has Abstract

pub_date

1996-06-04 00:00:00

pages

7051-7

issue

22

eissn

0006-2960

issn

1520-4995

pii

bi952857s

journal_volume

35

pub_type

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