Evaluation of the role of xanthine oxidase in myocardial reperfusion injury

Susan L. Thompson-Gorman, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

The free radical-generating enzyme xanthine oxidase has been hypothesized to be a central mechanism of the injury which occurs in postischemic tissues; however, its importance remains controversial. Much attention has focused on the role of this enzyme in myocardial reperfusion injury. While xanthine oxidase has been observed in ischemic tissue homogenstes, the presence and importance of radical generation by the enzyme in intact tissues are unknown. Therefore, we performed electron paramagnetic resonance, nuclear magnetic resonance and hemodynamic studies to measure the presence and significance of xanthine oxidasemediated free radical generation in the isolated rat heart. When isolated perfused rat hearts were reperfused after 30 min of global ischemia, myocardial function and coronary flow were significantly improved in the presence of the definitive xanthine oxidase blocker oxypurinol. Free radical concentrations measured by spin-trapping with 5,5′-dimethyl-l-pyrroline-N-oxide were significantly decreased by oxypurinol and the energetic state of the heart was improved as reflected by an increased recovery of phosphocreatine and a higher phosphocreatine/Pi ratio. ATP recovery, however, was not altered, indicating that the improved functional and metabolic state of the heart was not due to ATP salvage. Spectrophotometric assays for the enzyme showed an increase in the amount of xanthine oxidase relative to dehydrogenase following ischemia, and a total available xanthine oxidase pool in the rat heart of approximately 150 milliunits/g of protein. Thus, xanthine oxidase is a significant source of the oxidative injury which occurs upon reperfusion of the ischemic rat heart.

Original languageEnglish (US)
Pages (from-to)6656-6663
Number of pages8
JournalJournal of Biological Chemistry
Volume265
Issue number12
StatePublished - 1990

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Myocardial Reperfusion Injury
Xanthine Oxidase
Rats
Oxypurinol
Free Radicals
Phosphocreatine
Enzymes
Tissue
Adenosine Triphosphate
Spin Trapping
Salvaging
Recovery
Xanthine
Electron Spin Resonance Spectroscopy
Wounds and Injuries
Enzyme Assays
Hemodynamics
Oxides
Reperfusion
Myocardial Ischemia

ASJC Scopus subject areas

  • Biochemistry

Cite this

Thompson-Gorman, S. L., & Zweier, J. L. (1990). Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. Journal of Biological Chemistry, 265(12), 6656-6663.

Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. / Thompson-Gorman, Susan L.; Zweier, Jay L.

In: Journal of Biological Chemistry, Vol. 265, No. 12, 1990, p. 6656-6663.

Research output: Contribution to journalArticle

Thompson-Gorman, SL & Zweier, JL 1990, 'Evaluation of the role of xanthine oxidase in myocardial reperfusion injury', Journal of Biological Chemistry, vol. 265, no. 12, pp. 6656-6663.
Thompson-Gorman, Susan L. ; Zweier, Jay L. / Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 12. pp. 6656-6663.
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