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1989 Fiscal Year Final Research Report Summary

Role of oxygen free radicals in reperfusion myocardial injury

Research Project

Project/Area Number 63480227
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University School of Medicine

Principal Investigator

TADA Michihiko  Osaka University School of Medicine, Professor, 医学部, 教授 (90093434)

Co-Investigator(Kenkyū-buntansha) HOSHIDA Shiro  Osaka University School of Medicine, Research Fellow, 医学部附属病院, 医員
KADOMA Masaaki  Osaka University School of Medicine, Research Fellow, 医学部附属病院, 医員
KUZUYA Tsunehiko  Osaka University School of Medicine, Assistant Professor, 医学部, 助手 (80150340)
Project Period (FY) 1988 – 1989
KeywordsReperfusion injury / Oxygen free radical / Arachidonate lipoxygenase / Electron spin resonance / Cultured myocyte / Reoxygenation injury
Research Abstract

To define the relationship between oxygen-derived free radical (oxy-radical) generation in the reperfused ischemic myocardium and the progression of myocardial damage, we measured oxy-radical generation in the ischemic myocardium and the propagating infarct size in a canine coronary occlusion (90 minutes)-reperfusion model. We used electron paramagnetic resonance (EPR) spin trapping techniques (5,5'-dimethyl-l-pyrroline-n-oxide, DMPO) to detect oxy-radicals in the rapidly frozen myocardial samples taken by needle biopsy. There was no detectable generation of DMPO adducts in the normal myocardium before and after reperfusion. In the reperfused ischemic myocardium, EPR signals of DMPO-OOH (superoxide anion) and DMPO-OH (hydroxyl radical) were detected, with peak concentrations at 1 hour after reperfusion for DMPO-OOH and at 3 hours after reperfusion for DMPO-OH, respectively. These DMPO adducts were also detected during the early phase (15 seconds) of reperfusion, but the concentrations … More of these signals were much less than those during the late phase of reperfusion.
Treatment with human recombinant superoxide dismutase (2.5 mg/kg/hour) and catalase (2.5 mg/kg/hour) during the course of the experiments abolished DLIPO-OOH formation but had little effect on DMPO-OH formation. Infarct size (percent of risk area infarcted), quantified by a dual staining method using Evans blue dye and triphenyltetrazolium chloride, was 18.3 <plus-minus> 4.8% (mean <plus-minus> SEM) at 90 minutes of occlusion. After reperfusion, infarct size increased to 43.6 <plus-minus> 7.2% at 5 hours of reperfusion. These results indicate that a greater magnitude of oxy-radical generation was sustained in the ischemic myocardial tissue during the late phase (1-3 hours) of reperfusion, associated with the progression of myocardial infarction. The concurrent appearance of oxy-radicals and progressive infarction may support the view that a chain reaction of oxy-radicals contributes to the propagation of myocardial cell damage in the postischemic Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Tada M et al.: "Arachidonate metabolism in myocardial ischemia and reperfusion." J.Mol.Cell.Cardiol.20. 135-143 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuzuya T et al.: "Polymorphonuclear leukocyte activity and ventricular arrhythmia in acute myocardial infarction." Am.J.Cardiol. 62. 868-872 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuzuya T et al.: "Role of free radicals and neutrophils in canine myocardial reperfusion injury:myocardial salvage by a novel free radical scavenger,2-0-octadecylascorbid acid." Cardiovasc.Res.23. 323-330 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hoshida S et al.: "Attenuation of neutrophil function by inhibitors of arachidonate metabolism reduces the extent of canine myocardila infarction." Am.J.Cardiol.63. 24E-28E (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishida M et al.: "Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries." Circ.Res.66. 253-258 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuzuya T et al.: "Detection of oxygen-derived free radical generation in the canine postischemic heart during late phase of reperfusion." Circ.Res.(in press). 66. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 多田道彦: "プロスタグランジン" 化学同人, 166 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tada M, Kuzuya T, Hoshida S, Nishida M.: "Arachidonate metabolism in myocardial ischemia and reperfusion." J. Mol. Cell. Cardiol. 20:135-143, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuzuya T, Hoshida S, Suzuki K, Sasaki T, Kitabatake A, Kamada T, Minamino T, Tada M.: "Polymorphonuclear leukocyte activity and ventricular arrhythmia in acute myocardial infarction." Am. J. Cardiol. 62:868-872, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuzuya T, Kimura Y, Hoshida S, Kodama K, Nakamura N, Hamanaka Y, Kitabatake A, Kamada T, Tada M.: "The effect of CV-4151, a selective inhibitor of thromboxane synthetase, on prostanoid formation and platelet aggregation in humans." Cardiovasc. Drug. Ther. 2:693-700, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuzuya T, Hoshida S, Nishida M, Kim Y, Fuji H, Kitabatake A, Kamada T, Tada M.: "Role of free radicals and neutrophils in canine myocardial reperfusion injury: myocardial salvage by a novel free radical scavenger, 2-octadecylascorbic acid." Cardiovasc. Res. 23:323-330, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshida S, Kuzuya T, Nishida M, Kim Y, Kitabatake A, Kamada T, Tada M.: "Attenuation of neutrophil function by inhibitors of arachidonate metabolism reduces the extent of canine myocardial infarction." Am. J. Cardiol. 63:24E-28E, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishida M, Kuzuya T, Hoshida S, Kim Y, Fuji H, Kitabatake A, Kamada T, Tada M.: "Polymorphonuclear leukocytes induced vasoconstriction in isolated canine coronary arteries." Circ. Res. 66:253-258, 1990.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuzuya T, Hoshida S, Kim Y, Nishida M, Fuji H, Kitabatake A, Tada M, Kamada T.: "Detection of oxygen-derived free radical generation in the canine postischemic heart during late phase of reperfusion." Circ. Res. 66:1990.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-26  

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