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Pharmacological control of myocardial contractile function on myocardial stunning

Research Project

Project/Area Number 13470322
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNagasaki University

Principal Investigator

SUMIKAWA Koji  Nagasaki University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (60028660)

Co-Investigator(Kenkyū-buntansha) HARA Tetsuya  Nagasaki University, University Hospital of Medicine and Dentistry, Assistant professor, 医学部・歯学部附属病院, 講師 (50304952)
CHO Sungsam  Nagasaki University, University Hospital of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (90325655)
MIYOSHI Hiroshi  Nagasaki University, University Hospital of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (90332858)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2001: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsmyocardial ischemia / myocardial stunning / heart failure / coronary circulation / myocardial portection / contractile function / preconditioning / anesthetics / 虚血再灌流障害 / プレコンディショニング / プロポフォール / 交感神経β作動薬 / 微小塞栓 / デキサメデトミジン / 低酸素症 / Na^+ / Ca^<++>交換機構阻害薬 / 交感神経α_2作動薬 / KB-R7943 / 心筋 / スタニング / 吸入麻酔薬 / プロテインキナーゼC
Research Abstract

This study was carried out to investigate the mechanisms of myocardial stunning and to establish the pharmacological therapeutic method for myocardial stunning using the computer-based cardiovascular measurement system including the analysis of left ventricular pressure-volume relationship.
We investigated the hemodynamic and cardioprotective effects of sevoflurane or KB-R7943, a Na^+/Ca^<2+> exchanger inhibitor, on myocardial stunning in dogs. Sevoflurane has a cardioprotective effect mediated through activation of mitochondrial KATP channels and independent of coronary blood flow or reduction in cardiac work. KB-R7943 improves myocardial contractile dysfunction after ischemia-reperfusion in a dose-dependent, manner, and has no effect on coronary and systemic hemodynamics. We investigated the effects of propofol on myocardial contractility and oxygen balance in acute ischemic myocardium, using coronary microembolization model in dogs. Propofol causes a greater decrease in the contracti … More lity of acute ischemic myocardium as compared with normal myocardium, and oxygen imbalance is not involved in the mechanism of this propofol's action.
We demonstrated that overexpression of Glutaredoxin protected myocardium from hydrogen peroxide-induced apoptosis by regulating the redox state of Akt. Glutaredoxin plays an important role in protecting myocardium from oxidative stress.
We investigated the hemodynamic actions of dantrolene during propofol anesthesia. Dantrolene reverses the hypotensive action produced by propofol and causes an increase in coronary blood flow with a decrease in coronary vascular resistance. We investigated the effects of dexmedetomidine and propofol on the response of heart rate to intravenous isoproterenol. Dexmedetomidine but not propofol enhances the heart rate response to the continuous intravenous infusion of isoproterenol. We investigated the interaction of MCI-154, a calcium sensitizer, and isoflurane on myocardial contractility in chronically instrumented dogs after pharmacological autonomic nervous system activity blockade. MCI-154 increases myocardial contractility and decreases coronary vascular resistance without changing calculated myocardial oxygen consumption during both the conscious state and isoflurane anesthesia. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (40 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (34 results) Publications (6 results)

  • [Journal Article] Cardioprotective effects of KB-R7943, a novel inhibitor of Na^+/Ca^<2+> exchanger, on stunned myocardium in anesthetized dogs2005

    • Author(s)
      Osamu Yoshitomi
    • Journal Title

      J Anesth (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of the dogs2005

    • Author(s)
      Takuji Maekawa
    • Journal Title

      J Anesth (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Cardioprotective effects of KB-R7943, a novel inhibitor of Na^+/Ca^<2+> exchanger, on stunned mvocardium in anesthetized dogs.2005

    • Author(s)
      Yoshitomi O, Akiyama D, Hara T, Cho S, Tomiyasu S, Sumikawa K
    • Journal Title

      J Anesth (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of the dogs.2005

    • Author(s)
      Maekawa T, Cho S, Takahashi S, Hara T, Tomiyasu S, Makita T, Sumikawa K
    • Journal Title

      J Anesth (in press)

    • NAID

      10015697102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The interaction of MCI-154, a calcium sensitizer, and isoflurane on systemic and coronary hemodynamics in chronically instrumented dogs2004

    • Author(s)
      Shunji Takahashi
    • Journal Title

      Anesth Analg 98

      Pages: 30-36

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs2004

    • Author(s)
      Osamu Yoshitomi
    • Journal Title

      Anesthesiology 101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The interaction of MCI-154, a calcium sensitizer, and isoflurane on systemic and coronary hemodynamics in chronically instrumented dogs.2004

    • Author(s)
      Takahashi S, Cho S, Ham T, Ureshino H, Tomiyasu S, Sumikawa K
    • Journal Title

      Anesth Analg 98

      Pages: 30-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs.2004

    • Author(s)
      Yoshitomi O, Hara T, Akiyama D, Oshibuchi M, Sumikawa K
    • Journal Title

      Anesthesiology 101

    • NAID

      120006985371

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The protective effect of isoflurane against renal ischemia/reperfusion injury in rats2003

    • Author(s)
      Hiroshi Miyoshi
    • Journal Title

      Anesthesiology 96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Glutaredoxin exerts an antiapoptotic effect by regulating the redox state of Akt2003

    • Author(s)
      Hiroaki Murata
    • Journal Title

      J Biol Chem 278

      Pages: 50226-50233

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Hemodynamic interactions of propofol and dantrolene in chronically instrumented dogs2003

    • Author(s)
      Sungsam Cho
    • Journal Title

      Anesth Analg 96

      Pages: 1369-1373

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Differential effects of the sedative agents on the heart rate response to intravenous isoproterenol infusion2003

    • Author(s)
      Guao Huan
    • Journal Title

      Acta Med Nagasaki 48

      Pages: 149-152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The effects of dexmedetomidine on left ventricular function and oxygen consumption during hypoxia and reoxygenation in isolated rat hearts2003

    • Author(s)
      Sungsam Cho
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Isoflurane inhibits NFkB activation in response to simulated ischemia in renal tubular cell line, LLC-PK12003

    • Author(s)
      Masanori Matsumoto
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Fentanyl protects stunned myocardium in dogs2003

    • Author(s)
      Tetsuya Hara
    • Journal Title

      Anesth Analg 96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Pharmacological preconditioning effect of isoflurane against renal ischemia/reperfusion injury in rats2003

    • Author(s)
      Hideo Hashiguchi
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A novel cardioprotection mechanism by antioxidant glutaredoxin via Akt signaling pathway2003

    • Author(s)
      Hiroaki Murata
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Glutaredoxin exerts an antiapoptotic effect by reaulatina the redox state of Akt.2003

    • Author(s)
      Murata H, Ihara Y, Nakamura H, Yodoi J, Sumikawa K, Kondo T
    • Journal Title

      J Biol Chem 278

      Pages: 50226-50233

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Hemodynamic interactions of propofol and dantrolene in chronically instrumented dogs.2003

    • Author(s)
      Cho S, Zhang S, Ureshino H, Ham T, Tomiyasu S, Sumikawa K
    • Journal Title

      Anesth Analg 96

      Pages: 1369-1373

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Differential effects of the sedative agents on the heart rate response to intravenous isonroterennl infusion.2003

    • Author(s)
      Huan G, Takahashi S, Cho S
    • Journal Title

      Acta Med Nagasaki 48

      Pages: 149-149

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The effects of dexmedetomidine on left ventricular function and oxygen consumption during hypoxia and reoxygenation in isolated rat hearts.2003

    • Author(s)
      Cho S, Guo H, Hara T, Makita T, Sumikawa K
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Isoflurane inhibits NFkB activation in response to simulated ischemic in renal tubular cell line, LLC-PK1.2003

    • Author(s)
      Matsumoto M, Yamaguchi M, Hashiguchi H, Morooka H, Sumikawa K
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Fentanyl protects stunned myocardium in dogs.2003

    • Author(s)
      Hara T, Oshibuchi M, Yoshitomi O, Cho S, Tomiyasu S, Sumikawa K
    • Journal Title

      Anesth Analg 96

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Pharmacological preconditioning effect of isoflurane against renal ischemia/reperfusion injury in rats.2003

    • Author(s)
      Hashiguchi H, Morooka H, Miyoshi H, Matsumoto M, Sumikawa K
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] A novel cardioprotection mechanism by antioxidant glutaredoxin via Akt signaling pathway.2003

    • Author(s)
      Murata H, Ihara Y, Kondo T, Sumikawa K
    • Journal Title

      Anesthesiology 99

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Comparative effects of dexmedetomidine and propofol on myocardial contractility and oxygen balance during ischemic heart failure in dogs2002

    • Author(s)
      Takuji Maekawa
    • Journal Title

      America-Japan Anesthesia Congress 7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Comparative effects of dexmedetomidine and propofol on myocardial contractility and oxygen balance during ischemic heart failure in dogs.2002

    • Author(s)
      Maekawa T, Takahashi S, Cho S,. Hara T, Tomiyasu S, Sumikawa K
    • Journal Title

      America-Japan Anesthesia Congress 7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] The protective effect of isoflurane against renal ischemia/reperfusion injury in rats.2002

    • Author(s)
      Miyoshi H, Morooka H, Tsujita T, Hashiguchi H, Sumikawa K
    • Journal Title

      Anesthesiology 96

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels2001

    • Author(s)
      Tetsuya Hara
    • Journal Title

      Anesth Analg 92

      Pages: 1139-1145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Anti-ischemic effects of JTV-519, a novel cardioprotective agents, on stunned myocardium in dogs2001

    • Author(s)
      Tetsuya Hara
    • Journal Title

      Anesthesiology 95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Propentofylline, an adenosine uptake inhibitor, enhanced ischemic preconditioning through heat shock protein 70 expression2001

    • Author(s)
      Kazuyuki Sakai
    • Journal Title

      Anesthesiology 95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels.2001

    • Author(s)
      Hara T, Tomiyasu S, Cho S, Fukusaki M, Sumikawa K
    • Journal Title

      Anesth Analg 92

      Pages: 1139-1145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Anti-ischemic effects of JTV 519, a novel cardioprotective agents, on stunned myocardium in dogs.2001

    • Author(s)
      Hara T, Takahashi S, Cho S, Tomiyasu S, Sumikawa K
    • Journal Title

      Anesthesiology 95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Propentofylline, an adenosine uptake inhibitor, enhances ischemic preconditioning through heat shock protein 70 expression.2001

    • Author(s)
      Sakai K, Shibata S, Shibata O, Abe K, Sumikawa K
    • Journal Title

      Anesthesiology 95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takuji Maekawa: "Cardioprotective Effects of KB-R7943, a Na+/Ca2+ Exchanger Inhibitor, on Stunned Myocardium in Dogs"Anesthesiology. 99-3A. A-689 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Huan Guo: "Effect of Dexmedetomidine on the Myocardial Contractility and Oxygen Consumption during the Myocardial Hypoperfusion in Isolated Rat"Anesthesiology. 99-3A. A-724 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sungsam Cho: "Anti-Ischemic Effects of JTV-519, a Novel Cardioprotective Agent, on Stunned Myocardium in Dogs"Anesthesiology. 99-3A. A-686 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osamu Yoshitomi: "Cardioprotective Effects of KB-R7943, a Na^+/Ca2^+ Exchanger Inhibitor, on Stunned Myocardium in Dogs"Anesthesiology. 97-3A. A-600 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shunji Takahashi: "Effect of Dexmedetomidine on the Myocardial Contractility and Oxygen Consumption during the Myocardial Hypoperfusion in Isolated Rat Hearts"Anesthesiology. 97-3A. A-684 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tetsuya Hara: "Anti-Ischemic Effects of JTV-519, a Novel Cardioprotective Agent, on Stunned Myocardium in Dogs"Anesthesiology. 95-3A. A-664 (2001)

    • Related Report
      2002 Annual Research Report

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

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