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Role of central nervous system in sympathetic circulatory regulation in chronic heart failure.

Research Project

Project/Area Number 09670706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

ASANIOI Hidetsugu  Toyama Medical and Pharmaceutical University, Hospital, Assistant Professor, 附属病院, 講師 (00150128)

Co-Investigator(Kenkyū-buntansha) TAKASHIMA Shutaro  Toyama Medical and Pharmaceutical University, Faculty of Medicine, Research Associate, 医学部, 助手 (50146586)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHeart failure / Sympathetic nerve activity / Central nervous system / Sleep apnea / Lung stretch reflex / Alpha 2 agonist / 睡眠リズム / 中枢性α_2受容体刺激薬 / 筋交感神経活動 / 呼吸制御 / 周波数伝達関数 / 中枢性α2受容体刺激薬 / 圧利尿
Research Abstract

To elucidate the role of central nervous system in sympathoexcitation in heart failure, we examined l) modulation of sympathetic tone by lung stretch reflex, 2) sleep rhythm and autonomic function, and 3) effects of central sympathoinhibition for heart failure treatment. Close coupling between the brain stem respiratory oscillator and the central sympathetic network was examined by dynamic nature of reflex sympathoinhibition by lung inflation in patients with heart failure. Patients with a higher sympathetic drive had a spontaneous shallow respiration, I.e., a decreased input to lung inflation reflex and a greater tidal volume required to suppress muscle sympathetic nerve activity, I.e., an increased sympathoinhibitory threshold. One of the mechanisms for the increased sympathoinhibitory threshold could involve an increased baseline sympathetic tone. An overnight sleep study revealed that central sleep apnea and resultant oxyhemoglobin desaturation occurred frequently during shallow sl … More eep. The grade of desaturation correlated well with the level of plasma norepinephrine concentration (r = 0.84, p<0.01). Thus, in patients with heart failure, the abnormal breathing patterns in awake and sleeping states could contribute to the sympathoexcitation through attenuated inhibitory and enhanced excitatory mechanisms. To evaluate the effects of central sympathoinhibition on clinical status of heart failure, we gave a central alpha-2-adrenergic agohist, guanfacine, to patients with various severity of heart failure. Low dose (0.25mg/day) of guanfacine dramatically suppressed muscle sympathetic nerve activity and plasma norepinephrine level and augmented parasympathetic nerve activity assessed by heart rate variability. Naturesis was exaggerated despite of a significant fall in blood pressure. These beneficial actions were observed only in patients with severe heart failure and higher sympathetic tone. These findings suggest that the central nervous system plays an causative role in sympathoexcitation in heart failure and that the central sympathoinhibition could provide a new therapeutic option in this disorder. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report

Research Products

(37 results)

All Other

All Publications (37 results)

  • [Publications] Wada O., Asanoi H., et al: "Quantitative evaluation of blood flow distribution to exercising and resting skeletal muscles in patients with cardiac dysfunction using whole-body thallium-201 scintigraphy"Clin. Cardiol.. 20. 785-790 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nozawa T., Igawa A., et al: "Dual-tracer assessment of coupling between cardiac sympathetic neuronal function and downregulation of β-receptors during development of hypertensive heart failure of rats"Circulation. 97. 2359-2367 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishise H., Asanoi H., et al: "Time course of sympathovagal imbalalnce and left ventricular dysfunction in conscious dogs with heart failure"J. Appl. Physiol.. 84. 1234-1241 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Joho S., Asanoi H., et al: "Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans. Asympathoexcitatory response to myocardial ischemia"J. Am. Coll. Cardiol. 34. 1924-1931 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ibrahim H.A.R., Asanoi H., et al: "Modulation of left ventricular diastolic distensibility by collateral flow recruitment during balloon coronary occlusion"J. Am. Coll. Cardiol. 34. 500-506 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Goso Y., Asaanoi H., et al: "Relationship between low-frequency cardiovascular variability and muscle sympathetic nerve activity in patients with cardiac dysfunction"J Cardiovasc Pharmacol. 34. S63-S67 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 麻野井英次: "臨床医のための循環器自律神経機能検査法"今泉勉編著 メディカルレビュー社. 249 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 能澤学、麻野井英次: "心不全治療"山沖和秀、百村伸一編集 メディカルレビュー社. 663 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Wada O., Asanori H., et al: "Quantitative evaluation of blood flow distribution to exercising and resting skeletal muscles in patients with cardiac dysfunction using whole-body thallium-201 scintigraphy."Clin. Cardiol.. 20. 785-790 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nozawa T., Igawa A., et al: "Dual-tracer assessment of coupling between cardiac sympathetic neuronal function and downregulation of β-receptors during development of hypertensive heart failure of rats."Circulation. 97. 2359-2367 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishise H., Asanoi H., et al: "Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure."J. Appl. Physiol.. 84. 1234-1241 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Joho S., Asanoi H., et al: "Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans. A sympathoexcitatory response to myocardial ischemia."J. Am. Coll. Cardiol.. 34. 1924-1931 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ibrahim H. A. R., Asanoi H., et al: "Modulation of left ventricular diastolic distensibility by collateral flow recruitment during balloon coronary occlusion."J. Am. Coll. Cardiol.. 34. 500-506 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Goso Y., Asanoi H., et al: "Relationship between low-frequency cardiovascular variability and muscle sympathetic nerve activity in patients with cardiac dysfunction."J Cardiovasc Pharmacol. 34 (Supple 4). S63-S67 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Joho S., Asanoi H., et al.: "Time varying spectral analysis of heart rate and left ventricular pressure variability during coronary occlusion in human: A sympathoexcitatory response to myocardial ischemia"J Am Coll Cardiol. 34. 1924-1931 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Remah HA., Asanoi H., et al.: "Modulation of left ventricular diastolic distensibility by collateral recruitment during balloon coronary occlusion"J Am Coll Cardiol. 34. 500-506 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Goso Y., Asanoi H., et al.: "Relationship between low-frequency cardiovascular variability and muscle sympathetic nerve activity in patients with cardiac dysfunction"J Cardiovasc Pharmacol. 34. S63-S67 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 麻野井英次: "心不全と自律神経機能"Cardiologist. 4. 887-895 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 麻野井英次: "慢性心不全に対するβ遮断薬"呼吸と循環. 47. 975-979 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 麻野井英次: "心疾患における運動と自律神経"Therapeutic Research. 20. 1733-1738 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 麻野井英次: "心臓病診療プラクティス20 心臓病診療の問題点を考える:現代から未来へ"文光堂(東京). 316 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 麻野井英次: "Today's therapy 2000 今日の治療指針"医学書院. 1580 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishise H,Asanoi H,et al: "Time course of sympathovagal balance and left ventricular dysfunction in conscious dogs with heart failure." J Appl Physiol. 84. 1234-1241 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nozawa T,Igawa A,et al: "Dual-tracer aassessment of coupling between cardiac sympathetic neuronal function and downregulation of beta-receptors during development of hypertensive heart failure of rats." Circulation. 97. 2359-2367 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Goso Y,Asanoi H,et al: "Relationship Between Low-frequency Cardiovascular Variability and Muscle Sympathetic Nerve Activity in Patients with Cardiac Dysfunction." J Cardiovasc Pharm. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 麻野井英次: "心不全における自律神経機能-評価法と臨床的意義" Medical Practice. 15. 1703-1706 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 麻野井英次: "心不全と自律神経機能異常" 自律神経. 35. 343-349 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 麻野井英次: "私のストラテジー:心不全治療の選択と新知見の影響" 心臓病NEWS & NEWS. 8. 20-21 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 麻野井英次: "吉川純一,松崎益徳(編),心臓病心療プラクティス:心不全を癒" 文光堂 東京, 358 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 麻野井英次: "北畠顕,小川聡,永井良三,堀正二(編) 循環機能検査ハンドブック" 中山書店 東京, 707 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wada O,Asanoi H, et al: "Quantitative evaluation of blood flow distribution to esercising and resting skeletal muscles in patients with cardiac dysfunction using whole-body thallium-201 scintigraphy." Clin Cardiol. 20. 785-790 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishise H,Asanoi H, et al: "Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure." J.Appl.Physiol.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 麻野井英次: "心不全の発症・展開機序について最近明らかになってきたこと 心不全と中枢神経:神経調節がどのような関連を持つか." Progress in Medicine. 17. 2649-2653 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 麻野井英次: "自律神経バランスと強心薬." Pharma Medica. 15(Sup.). 26-33 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 麻野井英次: "アンジオテンシンII受容体(AIIR)拮抗薬と心不全の治療." Therapeutic Research. 18(Sup.3). S838-S840 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 麻野井英次: "心不全.「臨床医のための循環器自律神経機能検査法」今泉勉編著" メディカルレビュー社,東京, 169-180 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 麻野井英次: "心不全における運動療法.「心不全治療」矢崎義雄監修,山沖和秀,百村伸一編集" メディカルレビュー社,東京, 413-420 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-03-31   Modified: 2016-04-21  

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