Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites

Shinobu Miki, Muhammad Ashraf, Samer Salka, Nicholas Sperelakis

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The direct effect of oxygen metabolites was studied on isolated perfused rat hearts. Superoxide anion (O2) and hydrogen peroxide (H2O2) were generated by adding purine (2.3 mm) and purified xanthine oxidase (0.06 U/ml) to Krebs-Henseleit buffer (pH 7.4). Xanthine oxidase was added to the purine-containing perfusate either near the aorta (group A, which gave H2O2 less than 10 μm) or at a distant point from the aorta (group B, which gave 250 to 300 μm H2O2). The generation rate of O2 was 31.7 ± 1.0 nmol/ml/min in the experimental conditions. Contractile function, tissue adenosine triphosphate (ATP), and ultrastructure were not affected in group A. In contrast, hearts in group B showed marked decrease in contractility ( +dP dt) to 24.4 ± 4.3% of control values. ATP levels were also markedly reduced from control values of 23.4 ± 0.7 to 7.4 ± 0.7 μmol/g dry tissue. Ultrastructure in group B hearts revealed "wavy" and disintegrated sarcolemma, depletion of glycogen deposits, and swelling and disruption of mitochondria. Release of the thiobarbituric acid reactive products including malondialdehyde was significant in the effluent (1.68 ± 0.17 nmol/min/g wet tissue). These changes were almost completely prevented by catalase, but not by superoxide dismutase and deferoxamine. Moreover, exogenous H2O2 perfusion (300 μm) showed results similar to group B hearts. These observations suggest that H2O2 plays a major role in the injury. O2- does not appear to damage hearts directly, although it is important as a precursor of H2O2 and other radical species including hydroxyl radical.

Original languageEnglish (US)
Pages (from-to)1009-1024
Number of pages16
JournalJournal of molecular and cellular cardiology
Volume20
Issue number11
DOIs
StatePublished - Dec 1988
Externally publishedYes

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Keywords

  • Catalase
  • Free radical damage
  • Heart contractility
  • Hydrogen peroxide
  • Lipid peroxidation
  • Oxygen metabolites
  • Superoxide anion
  • Superoxide dismutase
  • Xanthine oxidase

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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