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Involvement of centhrachen-excitation feedback mechanism in arrhythmia in hear failure

Research Project

Project/Area Number 12670646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Tsukuba

Principal Investigator

YAMAGUCHI Iwa  University of Tsukuba, Institute of Clinical Medicine, Professor, 臨床医学系, 教授 (30111389)

Co-Investigator(Kenkyū-buntansha) MIYAUCHI Takashi  University of Tsukuba, Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (60222329)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsarrhythemia / heart failure / ion channel / electrical excitation / mechanical contraction / feed back / interaction / human and animals / 不全心筋 / 自律神経システム / 機械的收縮機構
Research Abstract

The "contraction-excitation feedback" mechamsm. exists in the heart. The mechanical stress has been reported to affect the. process of electrical excitation in the heart. This phenomenon is called to be "contraction-excitation feedback". Although it has been considered that the stretch activated ion channel is involved in its mechanisms, the precise mechanism is unclear.We measured QT-interval as an indicator of electrical excitation in various conditions such as pressure-overload to the left ventricle, valsalva stimulation, dysopyramide application. Furthermore, we also studied myocardial endothelin-1 and contraction-excitation feedback.
Cardiac myocytes as well as vascular endothelium produce othelin (ET)-1. In the heart, ET-1 induces myocardial hypertrophy and causes cellular injury of cardiac myocytes. In this study, we investigated roles of ET-1 in heart diseases such as chronic heart failure (CHF) and cardiac hypertrophy. We used coronary artery-ligated rat modelas a CHF model ani … More mal (CHF rats). It was revealed that production of ET-1 (both peptide and mRNA levels) is increased in the failing heart of the CHE rats. We also obtained the data that the upregulated myocardial ET-1 system may play an aggravating role in the progression of CHF, because long-term (12 weeks) treatment with the ET receptor antagonist BQ-123 greatly improved survival rate of CHE rats. Twelve weeks after BQ-123 application, survival rate of the CHF rats treated with BQ-123 (CHF-BQ rats) was markedly higher than that of the CHF rats tre4ted with saline alone (CHF-saline rats). BQ-123 treatment effectively prevented unfavorable ventricular remodeling of the CHF rats. In the hypertrophied left ventricle of the aorta-banded rats, the expression of ET-1 mRNA was significantly increased. Treatment with BQ-123 for 7 days significantly reduced cardiac hypertrophy of the aorta-banded rats. In these rats treated with BQ-123, the expression of mRNA of myocardial ion channels was altered.
These data suggest that contraction-excitation feedback mechanism is involved in arrhythmias in heart failure in experimental animals and in humans. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] S.Yamada, et al.: "Calculating integral values of the cardiac magnetic field is more sensitive to repolarization abnormalities than conducting electrocardiogram"Computers in Cardiology. Vol.27. 371-373 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Miyauchi, et al.: "Endothelin-1 and right sides heart failure in rats."Journal of Cardiovascular Pharmacology. Vol.36. S327-S330 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.Sakai, T.Miyauchi, I.Yamaguchi: "Long-term endothelin receptor antagonist administration improves alterations in expression of various cardiac genes in failing myocardium of rats with heart failure."Circulation. Vol.101 No.24. 2849-2853 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada S, et al.: "Evaluating ventricular repolarization abnormalities in the at-rest phase in ischemic heart diseases by using magnoto-cardiograms."Biomedizinische Technik. Vol.46. 47-49 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada S, Kuga K, Yamaguchi I.: "Torsade depointes induced by intrarenous and long-term oral amiodarone therapy in a patient with a dilated cardiomyopathy."Japanese Circulation Journal. Vol.65. 236-238 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iemitsu M, Miyauchi T, et al.: "Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat."American Journal of Physiology. Vol.281. R2029-R2036 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 山口 巖, 他: "納得できる心電図の読み方(山口巖編)"メジカルセンス社. 255 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satsuki Yamada, Keiji Tsukada, Tsuyoshi Miyashita, Iwao Yamaguchi: "Calculating integral values of the cardiac magnetic field is more sensitive to repolarization abnormalities than conducting electrocardiograms."Computers in Cardiology. 27. 371-373 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyauchi T, Sato R, Sakai S, Kobayashi T, Ueno M, Kondo H, Kawano S, Goto K, Yamaguchi I: "Endothelin-1 and right-sided heart failure in rats: Effects of an endothelin receptor antagonist on the failing right ventricle."Journal of Cardiovascular Pharmacology. 36. S327-S330 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sakai S, Miyauchi T, Yamaguchi I: "Long-term endothelin receptor antagonist administration improves alterations in expression of various cardiac genes in failing myocardium of rats with heart failure."Circulation. 101. 2849-2853 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satsuki Yamada, Keiji Tsukada, Tsuyoshi Miyashita, Shigeyuki Watanabe, Iwao Yamaguchi: "Evaluating ventricular repolarization abnormalities in the at-rest phase in ischemic heart disease by using magnetocardiograms."Biomedizinische Technik. 46. 47-49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satsuki Yamada, Keisuke Kuga, Iwao Yamaguchi: "Torsade de pointes induced by intravenous and long-term oral amiodarone therapy in a patient with a dilated cardiomyopathy."Jpn Circ J. 65. 236-238 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iemitsu.M, Miyauchi T, Maeda S, Sakai S, Kobayashi T, Fujii N, Miyazaki H, Matsuda M, Yamaguchi I: "Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat."American Journal of Physiology. 281. R2029-R2036 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada S, et al.: "Evaluating ventricular repolarization abnormalities in the at-rest phase in ischemic heart diseases byusing magnoto-cardioyrams"Biomedizinische Technik. vol46. 47-49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada S, Kuga K, Yamaguchi I.: "Torsade depointes induced by intrarenous and long-term oral amiodarone therapy in a patient with a dilated cardiomyopathy"Japanese Czrcalation Journal. vol65. 236-238 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li A et al.: "Effects of linear ablation at the isthmus between the tricaspid annulus and inferior rena cava for atial flutter on autonomic nerrous activity"Japanese Circulation Journal. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kakinuma Y, Miyauchi T et al.: "Novel molecular mechanism of increased mycardial endothelin-1 expression in the failing heart in volving the transcriptional factor hyperia-inducible factor-12 induced for myocardial energy metabolism"Circulation. vol103. 2387-2394 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yuki K, Miyauchi T et al.: "Endothelin-1 production is enhanced by rotenone, a mitochondrial complex I inhibitor, in cultured rat cardiomyocytes"Journal of Cerdiouascular Phamacdogy. vol38. 850-858 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iemitsu M, Miyauchi T et al.: "Physiological and pathological cardiar hyper trophy in drecl different molecular phonotypes in the rat"American Journal of Physiology. vol281. R2029-R2036 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山口 巖 他: "納得できる心電図の読み方"メジカルセンス社(山口 巖 編). 255 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Yamada, et al.: "Calculating integral ralues of the cardiac magnetic field is move sensitive to repolarization abnormalites than conducting electrocardiogph"Computers in Cardiology. vol.27. 371-373 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Hiyauchi, et al. : "Endothelin-1 and right sided heart failure in rats,"Journal of Cardiomuscular Pharmacology. vol 36. S327-S330 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Tsukada, et al.: "Magnetocardiographic mapping characteristic for diagnosis of ischemic heart diseases"Computers in Cardzology. vol.27. 505-508 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M,Iemitsu,T.Miyauchi, et al.: "Intense exercise causes disease in expression of both endithelial NO synthase and tissue NO_x level in hearts."American Journal of physiology . vol 279. R951-R959 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Sakat,T.Miyanchi,I,Yamaguchi.: "Long-term endothelin receptor an tagonist administration improve alterations in oxpression of various cardiac genes in fuiling myocardium of rats with neart faih"Circulation. vol 101 No.24. 2849-2853 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Murahoshi,T.Miyauchi, et al.: "Impairment of cardiac euergy metabolism in rivo causes hemoaynam abnormality and increases cardial expression of preproendothelin-1 mRNA"Journal of Cardiovascular Plarmacolosy. vol 36. S128-S131 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.MiyauchiY.Sugishita: "Heart failure ; Frontiers in Cardiology"Springer-rerlag (Edited by A.Kita batake, S.Sasayama, G.S, Frantis). 261 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 横田倫子,宮内卓: "高血圧ナビゲーター"メディカルレビュー社(荻原俊男 編). 286 (2000)

    • Related Report
      2000 Annual Research Report

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

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