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OXIDATIVE STRESS AND REPERFUSION INJURY OF HEART

Research Project

Project/Area Number 13671414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKINKI UNIVERSITY

Principal Investigator

NOJIMA Takehisa  KINKI UNIVERSITY, MEDICAL SCHOOL, ASSISTANT PROFFESSOR, 医学部, 講師 (00319740)

Co-Investigator(Kenkyū-buntansha) TOIYOKUNI Shinya  KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学研究科, 助教授 (90252460)
KOMEDA Masashi  KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 医学研究科, 教授 (20303810)
NISHIWAKI Noboru  KINKI UNIVERSITY, MEDICAL SCHOOL, PROFFESSOR, 医学部, 教授 (70319739)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsMYOCARDIAL INFARCTION / OXID ATIVE STRESS / APOPTOSIS / 再灌流障害 / 心筋
Research Abstract

Objective: Heart failure after MI is associated with oxidative stress. We studied spaciotemporal alteration of LV oxidative stress related to cell damage, LV function, and apoptotic change after MI.
Methods: LAD in SD rats was ligated. Heart was dissected 0, 3, 6, 12, 24, 48 hours, and 1, 2, 4 weeks after ligation. LV function was examined by echocardiography (SONOS 5500【○!R】), in the same time course. Oxidative stress was assessed by immunohistochemistry; determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) by HPLC-ECD, and cell injury was detected by nicotinamide adenine dinucleotide (NAD) level as coenzyme of ADP-ribose polymerase (PARP). Apoptotic change of the hearts was detected by TUNEL procedure.
Results: Soon after MI, oxidative stress as shown by 8-OHdG was intense, in 24 hours, cardiomyocytes were necrotized in the MI area. However, oxidative stress reincreased at 2 weeks [8-OHdG/dG×10^5: 0 91±0.04 (p<0.01) in Remote Areas, 1,16+0.19 (p<0.05) in Near Area]; it remained high o … More nly in Near Area at 4 weeks [1.18 + 0.76 (p<0.05)](Fig.). The peak of PARP was 6 hour after MI, with no second peak. The second peak had relationship with LV disfunction and enlargement. NAD decreased immediately and 1/10 of normal 12 hour after MI. It was normalized 2 weeks after MI. Three hours after the ligation of the coronary artery, few apoptotic cardiomyocytes were observed in the MI area, and scarcely any were observed in any area from 6 hours to 1 week. However, 2 to 4 weeks after the operation, cardiomyocytes in the peri-MI area showed apoptosis, suggesting that loss of cardiomyocytes occurred due to apoptosis induced by oxidative DNA damage.
Conclusion: Repair of DMA by PARP was maximal 6-12 hours after MI and so did 8-OHdG. Only 8-OHdG had the second peak 2 weeks after MI, and cardiomyocytes in Near Area remained oxidatively stressed even 4 weeks after MI. The first peak implies acute damage of DNA by ischemia, and the second peak suggests continuing damage of cardiomyocytes in the course of LV remodeling, related to apoptosis of cardiomyocites. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Senri Miwa, S.Toyokuni, M.Komeda et al.: "Spaciotemporal Alteration of 8-hydroxy-2'-deoxyguanosine Levels in Cardiomyocytes After Myocardial Infarction in Rats"Free Radical Research. 36(8). 853-858 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Senri Miwa, S. Toyokuni, M. Komeda et al: "Spatiotemporal Alteration of 8-hydroxy-2'-deoryguanosine Levels in Cardiomyocytes After Myocardial Infarction in Rats"Free Radical Research. 36 (8). 853-858 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Senri Miwa, S.Toyokuni, M.Komeda et al.: "Spaciotemporal Alteration of 8-hyclroxy-2'-deoxyguanosine Levels in Cardiomyocytes After Myocardial Infarction in Rats"Free Radical Research. 36(8). 853-858 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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