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Monoamine oxidae-induced hydroxyl radical production and cardiomyocyte injury during myocardial ischemia-reperfusion

Research Project

Project/Area Number 26462774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

AKIYAMA Tsuyoshi  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (70202554)

Co-Investigator(Renkei-kenkyūsha) INAGAKI Tadakatsu  独立行政法人国立循環器病研究センター, 血管生理学部, 上級研究員 (20638366)
SHIMIZU Shuji  独立行政法人国立循環器病研究センター, 循環動態制御部, 上級研究員 (80443498)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords心臓 / 虚血・再灌流 / モノアミン / ヒドロキシラジカル / マイクロダイアリシス法 / モノアミンオキシダーゼ / 心虚血・再灌流 / ミオグロビン
Outline of Final Research Achievements

We applied microdialysis technique to the heart of anesthetized rats. Dialysate samples were collected during 30 min of induced ischemia followed by 60 min of reperfusion. We monitored dialysate 3,4-dihydrobenzoic acid (3,4-DHBA) concentration as an index of hydroxyl radical production using a trapping agent (4-hydroxybenzoic acid), and dialysate myoglobin concentration as an index of cardiomyocyte injury in the ischemic region. Dialysate 3,4-DHBA concentration increased during ischemia and further increased after reperfusion. Pargyline, a MAO inhibitor, suppressed the averaged increase in dialysate 3,4-DHBA concentration during ischemia and reperfusion. Dialysate myoglobin concentration increased during ischemia and further increased after reperfusion. Pargyline reduced the averaged dialysate myoglobin concentration during ischemia and reperfusion. MAO plays a significant role in hydroxyl radical production and cardiomyocyte injury during ischemia and after reperfusion.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Myocardial interstitial levels of serotonin and its major metabolite 5-hydroxyindole acetic acid during ischemia-reperfusion.2017

    • Author(s)
      Du CK, Zhan DY, Akiyama T, Inagaki T, Shishido T, Shirai M, Pearson JT.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 312(1) Issue: 1 Pages: H60-H67

    • DOI

      10.1152/ajpheart.00471.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monoamine oxidase-induced hydroxyl radical production and cardiomyocyte injury during myocardial ischemia-reperfusion in rats2016

    • Author(s)
      Tadakatsu Inagaki, Tsuyoshi Akiyama, Cheng-Kun Du, Dong-Yun Zhan, Misa Yoshimoto & Mikiyasu Shirai
    • Journal Title

      Free Radical Research

      Volume: 50 Issue: 6 Pages: 645-653

    • DOI

      10.3109/10715762.2016.1162300

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute arterial baroreflex-mediated changes in plasma catecholamine concentrations in a chronic rat model of myocardial infarction.2016

    • Author(s)
      Kawada T, Akiyama T, Li M, Zheng C, Turner MJ, Shirai M, Sugimachi M.
    • Journal Title

      Physiol Rep.

      Volume: 4(15) Issue: 15

    • DOI

      10.14814/phy2.12880

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guanfacine enhances cardiac acetylcholine release with little effect on norepinephrine release in anesthetized rabbits.2015

    • Author(s)
      Shimizu S, Kawada T, Akiyama T, Turner MJ, Shishido T, Kamiya A, Shirai M, Sugimachi M.
    • Journal Title

      Autonomic Neuroscience

      Volume: 187 Pages: 84-87

    • DOI

      10.1016/j.autneu.2014.11.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predominant Role of Neural Arc in Sympathetic Baroreflex Resetting of Spontaneously Hypertensive Rats2015

    • Author(s)
      Sata Y, Kawada T, Shimizu S, Kamiya A, Akiyama T, and Sugimachi M.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 3 Pages: 592-599

    • DOI

      10.1253/circj.CJ-14-1013

    • NAID

      130004927116

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet2015

    • Author(s)
      Abe C, Nagai Y, Yamaguchi A, Aoki H, Shimizu S, Akiyama T, Kawada T, Sugimachi M, Morita H
    • Journal Title

      American Journal of Physiology

      Volume: in press Issue: 8 Pages: H942-H950

    • DOI

      10.1152/ajpheart.00697.2014

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acute Effects of Arterial Baroreflex on Sympathetic Nerve Activity and Plasma Norepinephrine Concentration2014

    • Author(s)
      Kawada T, Akiyama T, Shimizu S, Sata Y, Turner MJ, Shirai M and Sugimachi M
    • Journal Title

      Autonomic Neuroscience

      Volume: 186 Pages: 62-68

    • DOI

      10.1016/j.autneu.2014.10.016

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myocardial interstitial levels of serotonin and its major metabolite, 5-hydroxyindole acetic acid, in in vivo rat heart2014

    • Author(s)
      Cheng-Kun Du, Dong-Yun Zhan, Tsuyoshi Akiyama, Takashi Sonobe, Tadakatsu Inagaki, Mikiyasu Shirai
    • Journal Title

      Life Sciences

      Volume: 117 Issue: 1 Pages: 33-39

    • DOI

      10.1016/j.lfs.2014.09.019

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of intravenous cariporide on release of norepinephrine and myoglobin releases during myocardial ischemia/reperfusion in rabbits.2014

    • Author(s)
      Sakurai S, Kuroko Y, Shimizu S, Kawada T, Akiyama T, Yamazaki T, Sugimachi M, Sano S.
    • Journal Title

      Life Science

      Volume: 114 Issue: 2 Pages: 102-106

    • DOI

      10.1016/j.lfs.2014.08.008

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy2014

    • Author(s)
      Cheng-Kun Du, Dong-Yun Zhan, Sachio Morimoto, Tsuyoshi Akiyama, Daryl O. Schwenke, Hiroshi Hosoda, Kenji Kangawa, Mikiyasu Shirai
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 2 Issue: 5

    • DOI

      10.1002/prp2.64

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Medetomidine Suppresses Cardiac and Gastric Sympathetic Nerve Activities but Selectively Activates Cardiac Vagus Nerve2014

    • Author(s)
      Shimizu S, Akiyama T, Kawada T, Kamiya A, Turner MJ, Yamamoto H, Shishido T, Shirai M, Sugimachi M
    • Journal Title

      Circulation Journal

      Volume: 78 Issue: 6 Pages: 1405-1413

    • DOI

      10.1253/circj.CJ-13-1456

    • NAID

      130003391129

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 拡張型心筋症ノックインマウスにおける心臓ノルエピネフリン動態異常2017

    • Author(s)
      戦冬雲、杜成坤、秋山剛、森本幸生、白井幹康、ピアソンジェームス
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 拡張型心筋症ノックインマウスに対するドネペジルの治療効果2017

    • Author(s)
      杜成坤、戦冬雲、森本幸生、秋山剛、白井幹康、ピアソンジェームス
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Central α2-Adrenergic Receptors, but notα2A-Receptor, Play a Key Role in Aortic Depressor Nerve Stimulation-induced Cardiac Parasympathetic Activation2017

    • Author(s)
      清水秀二、川田 徹、秋山 剛、福満雅史、宍戸稔聡、杉町 勝
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cardiac vagal control in knock-in mouse model of dilated cardiomyopathy.2016

    • Author(s)
      Dong-Yun Zhan, Cheng-Kun Du, Tsuyoshi Akiyama, Sachio Morimoto, Shuji Shimizu, Toru Kawada, Mikiyasu Shirai, James T Pearson.
    • Organizer
      AHA Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Medetomidine but not guanfacine enhances cardiac parasympathetic acetylcholine release during aortic depressor nerve stimulation.2016

    • Author(s)
      Shimizu S, Kawada T, Akiyama T, Fukumitsu M, Kamiya A, Shishido T, Sugimachi M.
    • Organizer
      ESC Congress 2016
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心虚血・再灌流研究におけるマイクロダイアリシス法の有用性2016

    • Author(s)
      秋山 剛
    • Organizer
      第54回日本生体医工学会大会
    • Place of Presentation
      富山市
    • Year and Date
      2016-04-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 心筋トロポニンT突然変異に起因する肥大型心筋症における拡張機能障害の分子メカニズム2016

    • Author(s)
      杜 成坤
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 心不全ラットにおけるノルアドレナリン再吸収阻害が交感神経活動に及ぼす影響2016

    • Author(s)
      川田 徹
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 拡張型心筋症における心臓迷走神経調節機能異常と新規治療薬の開発2016

    • Author(s)
      戦 冬雲
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 拡張型心筋症ノックインマウス生命予後に対するグレリンの治療効果2015

    • Author(s)
      戦 冬雲、杜 成坤、森本幸生、秋山 剛、ダリル シュウェンケ、細田洋司、寒川賢治、白井幹康
    • Organizer
      第92回日本生理学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 心房マイクロダイアリシス法による心臓自律神経活動の定量化と心不全治療のための心臓保護薬の検索2015

    • Author(s)
      清水秀二、川田 徹、秋山 剛、神谷厚範、宍戸稔聡、白井幹康、杉町 勝
    • Organizer
      第92回日本生理学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report
  • [Presentation] モノアミンオキシダーゼによる心筋虚血再灌流時のヒドロキシラジカル産生2015

    • Author(s)
      稲垣薫克、秋山 剛、戦 冬雲、杜 成坤、白井幹康
    • Organizer
      第92回日本生理学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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