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The Role of RhoA/Rho-kinase System in the Deterioration of Coronary Microcirculation in Ischemic Heart Disease

Research Project

Project/Area Number 14570674
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyushu University

Principal Investigator

ITO Akira (2003)  Kyushu University Hospital, Assist. Prof., 大学病院, 助手 (00360868)

毛利 正博 (2002)  九州大学, 医学部附属病院, 講師 (60264032)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  Kyushu University, Graduate School of Medical Sciences, Assoc. Prof., 大学院・医学研究院, 助教授 (00235681)
伊藤 昭  九州大学, 医学部附属病院, 医員
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsangina pectoris / coronary microvessel / coronary vasospasm / Rho-kinase / myocardial ischemia / 冠循環 / 微小循環 / 微小血管狭心症
Research Abstract

Effective treatment of patients with angina who have normal coronary arteriograms (microvascular angina) has not yet been established. Rho-kinase-mediated calcium sensitization of the myosin light chain in smooth muscle cells has been implicated as substantially contributing to vascular hyperconstriction. Accordingly, we sought to determine whether a potent Rho-kinase inhibitor fasudil prevents the occurrence of myocardial ischemia in patients with microvascular angina attributable to coronary microvascular spasm. We studied consecutive 18 patients with angina and normal epicardial coronaries in whom intracoronary acetylcholine (Ach) induced myocardial ischemia (ischemic electrocardiographic ahnges, myocardial lactate production, or both) without angiographically demonstrable epicardial coronary vasospasm. All patients underwent a second Ach challenge test after pretreatment with either saline (n=5) or fasudil (4.5mg intracoronarily, n=13). Myocardial ischemia was reproducibly induced by Ach in the saline group. In contrast, 11 of the 13 patients pretreated with fasudil had no evidence of myocardial ischemia during the second infusion of Ach (p<0.01). The lactate extraction ratio (median value [interquartile range]) during Ach infusion was improved by fasudil pretreatment, from -0.16 (-0.25 tp 0.04), to 0.09 (0.05 to 0.18) (p=0.0125). These results suggest that the inhibition of Rho-kinase may be a novel therapeutic strategy for this group of patients with microvascular angina.

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Mohri M, et al.: "Rho-Kinase Inhibition With Intracoronary Fasudil Prevents Myocardial Ischemia in Patients With Coronary Microvascular Spasm"Journal of American College of Cardiology. 41. 15-19 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 毛利正博: "処方-わたしの考え方:微小血管狭心症"臨床と研究. 79. 500-501 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 毛利正博ほか: "心臓微小循環"医学のあゆみ. 201. 751-756 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 毛利正博ほか: "Rhoキナーゼ阻害薬と狭心症"BIO Clinica. 17. 1159-1164 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 毛利正博ほか: "Rho-kinase阻害薬と狭心症"日本臨床. 61 Suppl 5. 874-879 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "PanVascular Medicine(分担執筆)"Springer-Verlag, Berlin. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimokawa H, et al.: "PanVascular Medicine(分担執筆)"Springer-Verlag, Berlin. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Rho-Kinase Inhibition With Intracoronary Fasudil Prevents Myocardial Isehemia in Patients With Coronary Microvascular Spasm."Journal of American College of Cardiology. 41. 15-19 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M: "Microvascular angina."Rinsho to Kenkyu. 79. 500-501 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Coronary microcirculation."Igaku no Ayumi. 201. 751-756 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Rho-kinase inhibitor and angina pectoris."BIO Clinica. 17. 1159-1164 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Rho-kinase inhibitor and angina pectoris."Nihon Rinsho. 61(Suppl 5). 874-879 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Coronary artery spasm clinical aspect (Lanzer P, Topol EJ, eds) Pan Vascular Medicine, Berlin"Springer-Verlag. 921-930 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimokawa H, et al.: "Coronary artery spasm basic aspect (Lanzer P, Topol EJ, eds)Pan Vascular Medicine, Berlin"Springer-Verlag. 921-930 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mohri M, et al.: "Rho-Kinase Inhibition With Intracoronary Fasudil Prevents Myocardial Ischemia in Patients With Coronary Microvascular Spasm"Journal of American College of Cardiology. 41. 15-19 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 毛利正博: "処方-わたしの考え方:微小血管狭心症"臨床と研究」. 79. 500-501 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 毛利正博ほか: "心臓微小循環"医学のあゆみ. 201. 751-756 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 毛利正博ほか: "Rhoキナーゼ阻害薬と狭心症"BIO Clinica. 17. 1159-1164 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 毛利正博ほか: "Rho-kinase阻害薬と狭心症"日本臨床. 61 Suppl 5. 874-879 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mohri M, et al.: "PanVascular Medicine(分担執筆)"Springer-Verlag, Berlin. 921-930 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimokawa H, et al.: "PanVascular Medicine(分担執筆)"Springer-Verlag, Berlin. 912-920 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akihiro Masumoto, et al.: "Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina"Circulation. 105. 1545-1547 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masahiro Mohri, et al.: "Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular angina"Journal of the American College of Cardiology. 41. 15-19 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masahiro Mohri, et al.: "Endogenous nitric oxide ameliorates myocardial ischemia in patients with hypertension and left ventricular hypertrophy"American Heart Journal. 143. 684-689 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 毛利正博: "Rhoキナーゼ阻害薬と狭心症"BIO Clinica. 17. 1159-1164 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 毛利正博: "冠動脈の臨床(分担執筆)"目本臨床社 (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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