Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites.
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 microM) or at a distant point from the aorta (group B, which gave 250 to 300 microM 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 mumol/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 microM) 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.
Miki
S
S
Department of Pathology, University of Cincinnati Medical Center, OH 45267.
Ashraf
M
M
Salka
S
S
Sperelakis
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013481:Superoxides / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D013481:Superoxides; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase