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MECHANISMS OF VENTRICULAR ARRHYTHMIAS IN HEART FAILURE

Research Project

Project/Area Number 08670782
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionSHIGA UNIVERSITY OF MEDICAL SCIENCE

Principal Investigator

ITO Makoto  SHIGA UNIVERSITY OF MEDICAL SCIENCE,ASSOCIATE PROFESSOR, 医学部, 講師 (70159911)

Co-Investigator(Kenkyū-buntansha) WADA Atsuyuki  SHIGA UNIVERSITY OF MEDICAL SCIENCE,ASSISTANT PROFESSOR, 医学部, 助手 (10273400)
SUGIMOTO Yoshihisa  SHIGA UNIVERSITY OF MEDICAL SCIENCE,ASSISTANT PROFESSOR, 医学部, 助手 (30216337)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsRAPID VENTRICULAR PACING / HEART FAILURE / ACTION POTENTIAL / VENTRICULAR ARRHYTHMIA / CARDIAC SYMPATHETIC NERVOUS SYSTEM / 交感神経機能 / Heart failure / Cardiac arrhythmia / Pacing / Action potential
Research Abstract

We have made a heart failure model with using rapid ventricular pacing in canine hearts. After ventricular pacing rate 270 bpm for 14 days, dogs showed congestive heart failure with enlarged heart, pleural effusion, and ascitis. Dogs exhibited abnormalities in neurohumoral factors such as increased ANP, BNP, enhanced renin-angiotensin-aldosterone system, and endotheline.
In dog hearts with heart failure, monophasic action potential duration recorded from ventricle was shorter compared with normal heart. This result was different from other chronic heart failure model with microsphare-induced ischemic dog hearts.
We have also made rapid pacing model in rabbit hearts. Ventricular pacing rate from 300 to 350 bpm shortened a duration of monophasic action potential in vivo. Shortening of action potential duration recovered by 4-aminopyridine which blocks the transient outward current (Ito). We concluded that short period of rapid ventricular pacing enhanced Ito. Such different results might b … More e affected by heart failure models and/or species.
Washout rate of 1-123 metaiodobenzylguanidine which reflects cardiac sympathetic neural function was greater in patients with ventricular tachycardia/fibrillation compared to the patients without ventricular tachycardia/fibrillation, although cardiac function was comparable between groups. with and without VT/VF.We concluded that cardiac sympathetic function was abnormal in the patients with malignant ventricular tachyarrhythmias compared to the patients without malignant ventricular tachyarrhythmias in chronic non-ischemic heart failure. Moreover, regional sympathetic imbalance reflected by heterogeneous washout of MIBG exists in symptomatic patients with long QT syndrome. Such abnormal sympathetic neural function can exacerbate malignant ventricular tachyarrhythmias in long QT syndrome. We also demonstrated that fatty acid metabolism was abnormal in coronary artery disease which is major cause of heart failure. Successful angioplasty restores fatty acid metabolism. Ischemia shortened ventricular action potential duration via activation of ATP-sensitive potassium channels. Opening of ATP-sensitive potassium channels preserves ischemic changes of epicardial ECG. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Atsushi Takaoka: "Nicorandil Improves Ischemic Changes in Epicardial ECG During Short-Term Coronary Occlusion by Opening ATP-Sensitive aotassium" Cardiovascular Drugs and Therapy. 11. 757-766 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yukiharu Maeda: "Chronic effects of ANG II antagonist in heart failure: Improvement of cGMP generation from ANP" American Journal of Physiology. 272. H2139-H2145 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shitaro Yoshida: "Improved Myocardial Fatty Acid Metabolism After Coronary Angioplasty in Chronic Coronary Artery" The Journal of Nuclear Medicine. 39. 933-938 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 中江 一郎: "ブタ虚血モデルにおけるNicorandilの心筋虚血改善作用" Therapeutic Research. 18. 157-169 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shintaro Yoshida, Makoto Ito, Kenichi Mitsunami and Masahiko Kinoshita: "Improved myocardial fatty acid metabolism after coronary angioplasty in chronic coronary artery disease" J Nucl Medicine. 39 (6). 933-938 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Atsushi Takaoka, Ichiro Nakae, Quan Liu, Kazumasa Yamamoto, Makoto Ito, Masahiko Kinoshita: "Nicorandil improves ischemic changes in epicardial ECG during short-term coronary occlusion by opening ATP-sensitive potassium channels in pigs" Cardiovasc Drugs Ther. 11. 757-766 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ichiro Nakae, Atsushi Takaoka, Quan Liu, Tetsuya Matsumoto, Yoshihisa Sugimoto, Masayuki Takahashi, Makoto Ito, Masahiko Kinoshita: "Anti-ischemic effects of ATP-sensitive potassium channel blocker, nicorandil, in porcine hearts" Therapeutic Research. 18 (3). 157-165 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yukiharu Maeda, Atsuyuki Wada, Takayoshi Tsutamoto, Daisuke Fukai, , and Masahiko Kinoshita: "Chronic effects of ANG II antagonist in heart failure : improvement of cGMP generation from ANP" American Journal of Physiology. 272 (heart Circ, Physiol.). H2139-H2145 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shintaro Yoshida, Makoto Ito: "Improved fatty acid Metabolism after PTCA in chronoc coronary artery disease" J Nuclear Medicine. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Takaoka, Makoto Ito: "Ncorandil improves ischemic changes on epicardial ECG during short-time coronary α clusion by opening ATP.senfa five K clume" Cardiorasc.Drugs Ther. 11. 757-766 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsuyuki Wada: "Comparison of the effects of selective andothlin ETA and ETB receptor antagonists in congestive heart failure" J of the American College of Cardiology. 30・5. 1385-1392 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Makoto Ito: "Efferent sympathetic and vagal innervation of the canine right ventricle." Circulation. 90. 1459-1468 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ito: "Glibenclamide enhances but pinacidil reduces attenuation in sympathetic responsiveness after acute coronary artery occlusion." Circulation Reserch. 75. 379-392 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ito: "Defibrillating shocks delivered to the heart impair efferent sympathetic responsiveness" Circulation. 88. 2661-2673 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ito: "Intrapericardial fluid modulates sympathetic denervation after coronary artery occlusion by wash out of ischemic metabolites." Circulation. 88. I-356 (1993)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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