| Project/Area Number |
63480227
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University School of Medicine |
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Principal Investigator |
TADA Michihiko Osaka University School of Medicine, Professor, 医学部, 教授 (90093434)
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| 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)
乾 誠 大阪大学, 医学部附属病院, 医員
星田 四朗 大阪大学, 医学部附属病院, 医員
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | Reperfusion injury / Oxygen free radical / Arachidonate lipoxygenase / Electron spin resonance / Cultured myocyte / Reoxygenation injury / 再酸素化心筋障害 / 活性酸素 / フリ-ラジカル / スピントラップ / アラキドン酸リポキシゲナーゼ代謝 / 化学発光法 |
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| 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
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