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Strategic Autonomic Nervous Control Using Artificial Brainstem to Cope With Obstinate Cardiovascular Diseases

Research Project

Project/Area Number 15200040
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionKYUSHU UNIVERSITY (2004-2005)
National Cardiovascular Center Research Institute (2003)

Principal Investigator

SUNAGAWA Kenji  Kyushu University, Graduate School of Medicine, Medical Sciences, Professor, 大学院・医学研究院, 教授 (50163043)

Co-Investigator(Kenkyū-buntansha) SUGIMACHI Masaru  National Cardiovascular Center research Institute, Department of Cardiovascular Dynamics, Director, 循環動態機能部, 部長 (40250261)
KAWADA Toru  National Cardiovascular Center research Institute, Department of Cardiovascular Dynamics, Laboratory chief, 循環動態機能部, 室長 (30243752)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥37,830,000 (Direct Cost: ¥29,100,000、Indirect Cost: ¥8,730,000)
Fiscal Year 2005: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2004: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2003: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Keywordsbionic medicine / electronic therapy / cute myocardial infarction / heart failure / cardiac remodeling / vagus / ortic depressor nerve / arterial baroreflex / 心筋梗塞 / 人工脳幹部 / 自律神経 / 抗炎症作用 / 冠動脈閉塞 / 生存率 / 交感神経 / 心機能 / 迷走神経刺激 / β遮断薬 / BNP
Research Abstract

In this study we demonstrated that controlling the autonomic tone arbitrarily by using an electronic artificial brainstem reduced the mortality and inhibited cardiac remodeling in the ischemia-induced heart failure model. In the electronic therapy targeting the vagus, a combination of the electronic treatment with beta-adrenergic inhibition showed more significant improvement, suggesting that the vagal effects are different from the beta-adrenergic inhibition. In the electronic therapy targeting the arterial baroreflex afferent pathway, vagotomy reduced the improvement of survival rate after acute myocardial ischemia, suggesting the importance of the vagal efferent pathway. Next, we speculated that anti-inflammatory effects through the abdominal vagus might contribute to the improvement of heart failure, and performed the electronic therapy in animals with abdominal vagal transection. The results indicate that the abdominal vagi contribute to the improvement of hemodynamics but not to … More the improvement of survival after myocardial ischemia. In parallel with these therapeutic experiments, we identified the dynamic characteristics of baroreceptor transduction and developed a new identification method for the arterial baroreflex central function. These studies should provide a basis necessary for integration of the artificial brainstem into the biological systems.
The above-mentioned bionic medicine using the artificial brainstem is a fusion of the state-of-the-art medicine and the cutting-edge engineering, and is unique in the medical history. Because the bionic medicine was able to improve the prognosis of heart failure via mechanisms different from ordinary pharmacological treatments of sympathetic inhibition, the present therapeutic strategy should have a great impact on the current medicine. Heart failure is a greatest medical agenda both socially and financially in advanced countries. Clinical application of the present research results is expected not only to cure patients but also to promote the economical efficiency in the society, directly leading to the invention of intellectual properties and new industries. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (54 results)

All 2006 2005 2004 Other

All Journal Article (51 results) Publications (3 results)

  • [Journal Article] Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release.2006

    • Author(s)
      Kawada T et al.
    • Journal Title

      Life Sci. 78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure.2006

    • Author(s)
      Uemura K et al.
    • Journal Title

      J Appl Physiol. 100

      Pages: 1278-1286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model : high-resolution optical mapping study.2006

    • Author(s)
      Aiba T et al.
    • Journal Title

      J Am Coll Cardiol 47

      Pages: 2074-2085

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Short-term electroacupuncture at Zusanli resets the arterial baroreflex neural arc toward lower sympathetic nerve activity.2006

    • Author(s)
      Michikami D et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reversible vagal blockade in conscious rats using a targeted delivery device.2006

    • Author(s)
      Zheng C et al.
    • Journal Title

      J Neurosci Methods (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release.2006

    • Author(s)
      Kawada T, Yamazaki T, Akiyama T, Li M, Ariumi H, Mori H, Sunagawa K, Sugimachi M.
    • Journal Title

      Life Sci. 78

      Pages: 882-887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure.2006

    • Author(s)
      Uemura K, Kamiya A, Hidaka I, Kawada T, Shimizu S, Shishido T, Yoshizawa M, Sugimachi M, Sunagawa K.
    • Journal Title

      J Appl Physiol. 100

      Pages: 1278-1286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular basis for trigger and maintenance of ventricular fibrillation in the Brugada syndrome model : high-resolution optical mapping study.2006

    • Author(s)
      Aiba T, Shimizu W, Hidaka I, Uemura K, Noda T, Zheng C, Kamiya A, Inagaki M, Sugimachi M, Sunagawa K.
    • Journal Title

      J Am Coll Cardiol 47

      Pages: 2074-2085

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Short-term electroacupuncture at Zusanli resets the arterial baroreflex neural arc toward lower sympathetic nerve activity.2006

    • Author(s)
      Michikami D, Kamiya A, Kawada T, Inagaki M, Shishido T, Yamamoto K, Ariumi H, Iwase S, Sugenoya J, Sunagawa K, Sugimachi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reversible vagal blockade in conscious rats using a targeted delivery device.2006

    • Author(s)
      Zheng C, Kawada T, Li M, Sato T, Sunagawa K, Sugimachi M.
    • Journal Title

      J Neurosci Methods (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prediction of circulatory equilibrium in response to changes in stressed blood volume.2005

    • Author(s)
      Uemura K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microdialysis separately monitors myocardial interstitial myoglobin during ischemia and reperfusion.2005

    • Author(s)
      Kitagawa H et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits.2005

    • Author(s)
      Kamiya A et al.
    • Journal Title

      J Physiol. 566

      Pages: 237-246

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-frequency oscillation of sympathetic nerve activity decreases during development of tilt-induced syncope preceding sympathetic withdrawal and bradycardia.2005

    • Author(s)
      Kamiya A et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Muscle sympathetic nerve activity averaged over 1 minute parallels renal and cardiac sympathetic nerve activity in response to a forced baroreceptor pressure change.2005

    • Author(s)
      Kamiya A et al.
    • Journal Title

      Circulation 112

      Pages: 384-386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dynamic and static baroreflex control of muscle sympathetic nerve activity(SNA)parallels that of renal and cardiac SNA during physiological change in pressure.2005

    • Author(s)
      Kamiya A et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits.2005

    • Author(s)
      Kawada T et al.
    • Journal Title

      Jpn J Physiol. 55

      Pages: 157-163

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prediction of circulatory equilibrium in response to changes in stressed blood volume.2005

    • Author(s)
      Uemura K, Kawada T, Kamiya A, Aiba T, Hidaka I, Sunagawa K, Sugimachi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microdialysis separately monitors myocardial interstitial myoglobin during ischemia and reperfusion.2005

    • Author(s)
      Kitagawa H, Yamazaki T, Akiyama T, Sugimachi M, Sunagawa K, Mori H.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits.2005

    • Author(s)
      Kamiya A, Kawada T, Yamamoto K, Michikami D, Ariumi H, Uemura K, Zheng C, Shimizu S, Aiba T, Miyamoto T, Sugimachi M, Sunagawa K.
    • Journal Title

      J Physiol. 566

      Pages: 237-246

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-frequency oscillation of sympathetic nerve activity decreases during development of tilt-induced syncope preceding sympathetic withdrawal and bradycardia.2005

    • Author(s)
      Kamiya A, Hayano J, Kawada T, Michikami D, Yamamoto K, Ariumi H, Shimizu S, Uemura K, Miyamoto T, Aiba T, Sunagawa K, Sugimachi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Muscle sympathetic nerve activity averaged over 1 minute parallels renal and cardiac sympathetic nerve activity in response to a forced baroreceptor pressure change.2005

    • Author(s)
      Kamiya A, Kawada T, Yamamoto K, Michikami D, Ariumi H, Miyamoto T, Uemura K, Sugimachi M, Sunagawa K.
    • Journal Title

      Circulation 112

      Pages: 384-386

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dynamic and static baroreflex control of muscle sympathetic nerve activity (SNA) parallels that of renal and cardiac SNA during physiological change in pressure.2005

    • Author(s)
      Kamiya A, Kawada T, Yamamoto K, Michikami D, Ariumi H, Miyamoto T, Shimizu S, Uemura K, Aiba T, Sunagawa K, Sugimachi M.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dynamic characteristics of carotid sinus pressure-nerve activity transduction in rabbits.2005

    • Author(s)
      Kawada T, Yamamoto K, Kamiya A, Ariumi H, Michikami D, Shishido T, Sunagawa K, Sugimachi M.
    • Journal Title

      Jpn J Physiol. 55

      Pages: 157-163

    • NAID

      10016882409

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Automated drug delivery system to control systemic arterial pressure, cardiac output, and left heart filling pressure in acute decompensated heart failure.2005

    • Author(s)
      Uemura K et al.
    • Journal Title

      J Appl Physiol (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Vagal stimulation suppresses ischemia-induced myocardial release interstitial norepinephrine release2005

    • Author(s)
      Kawada T et al.
    • Journal Title

      Life Sci 78・8

      Pages: 882-887

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prediction of circulatory equilibrium in response to changes in stressed blood volume.2005

    • Author(s)
      Uemura K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 289・1

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Myocardial interstitial choline and glutamate levels during acute myocardial ischaemia and local ouabain administration2005

    • Author(s)
      Kawada T et al.
    • Journal Title

      Acta Physiol Scand 184・3

      Pages: 187-193

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bezold-Jarisch reflex blunts arterial baroreflex via the shift of neural arc toward lower sympathetic nerve activity.2004

    • Author(s)
      Kashihara K et al.
    • Journal Title

      Jpn J Physiol. 54

      Pages: 395-404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A derivative-sigmoidal model reproduces operating point-dependent baroreflex neural arc transfer characteristics.2004

    • Author(s)
      Kawada T et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics.2004

    • Author(s)
      Kawada T et al.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via α-adrenergic mechanism.2004

    • Author(s)
      Miyamoto T et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 287

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adaptive predictive control of arterial blood pressure based on a neural network during acute hypotension.2004

    • Author(s)
      Kashihara K et al.
    • Journal Title

      Ann Biomed Eng. 32

      Pages: 1365-1383

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.2004

    • Author(s)
      Uemura K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 287

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel framework of circulatory equilibrium.2004

    • Author(s)
      Uemura K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats..2004

    • Author(s)
      Li M et al.
    • Journal Title

      Circulation 109

      Pages: 120-124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bionic epidural stimulation restores arterial pressure regulation during orthostasis.2004

    • Author(s)
      Yanagiya Y et al.
    • Journal Title

      J Appl Physiol. 97

      Pages: 984-990

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Muscle mechanoreflex induces the pressor response by resetting the arterial baroreflex neural arc.2004

    • Author(s)
      Yamamoto K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bezold-Jarisch reflex blunts arterial baroreflex via the shift of neural arc toward lower sympathetic nerve activity.2004

    • Author(s)
      Kashihara K, Kawada T, Li M, Sugimachi M, Sunagawa K.
    • Journal Title

      Jpn J Physiol. 54

      Pages: 395-404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics.2004

    • Author(s)
      Kawada T, Miyamoto T, Uemura K, Kashihara K, Kamiya A, Sugimachi M, Sunagawa K.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via α-adrenergic mechanism.2004

    • Author(s)
      Miyamoto T, Kawada T, Yanagiya Y, Inagaki M, Takaki H, Sugimachi M, Sunagawa K.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adaptive predictive control of arterial blood pressure based on a neural network during acute hypotension.2004

    • Author(s)
      Kashihara K, Kawada T, Uemura K, Sugimachi M, Sunagawa K.
    • Journal Title

      Ann Biomed Eng. 32

      Pages: 1365-1383

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.2004

    • Author(s)
      Uemura K, Kawada T, Sugimachi M, Zheng C, Kashihara K, Sato T, Sunagawa K.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel framework of circulatory equilibrium.2004

    • Author(s)
      Uemura K, Sugimachi M, Kawada T, Kamiya A, Jin Y, Kashihara K, Sunagawa K.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats.2004

    • Author(s)
      Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K.
    • Journal Title

      Circulation 109

      Pages: 120-124

    • NAID

      120001794314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bionic epidural stimulation restores arterial pressure regulation during orthostasis.2004

    • Author(s)
      Yanagiya Y, Sato T, Kawada T, Inagaki M, Tatewaki T, Zheng C, Kamiya A, Takaki H, Sugimachi M, Sunagawa K.
    • Journal Title

      J Appl Physiol. 97

      Pages: 984-990

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Muscle mechanoreflex induces the pressor response by resetting the arterial baroreflex neural arc.2004

    • Author(s)
      Yamamoto K, Kawada T, Kamiya A, Takaki H, Miyamoto T, Sugimachi M, Sunagawa K.
    • Journal Title

      Am J Physiol Heart Circ Physiol. 286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bezold-Jarisch reflex blunts arterial baroreflex via the shift of neural arc toward lower sympathetic nerve activity2004

    • Author(s)
      Kashihara K et al.
    • Journal Title

      Jpn J Physiol 54・4

      Pages: 395-404

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats2004

    • Author(s)
      Uemura K et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 287・6

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adaptive predictive control of arterial blood pressure based on a neural network during acute hypotension2004

    • Author(s)
      Kashihara K et al.
    • Journal Title

      Ann Biomed Eng 32・10

      Pages: 1365-1383

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bionic epidural stimulation restores arterial pressure regulation during orthostasis2004

    • Author(s)
      Yanagiya Y
    • Journal Title

      J Appl Physiol 97・3

      Pages: 984-990

    • Related Report
      2004 Annual Research Report
  • [Publications] Meihua Li: "Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats"Circulation. 109・1. 120-124 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazunori Uemura: "A novel framework of circulatory equilibrium"Am J Physiol Heart Circ Physiol. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toru Kawada: "A derivative-sigmoidal model reproduces operating-point dependent baroreflex neural arc transfer characteristics"Am J Physiol Heart Circ Physiol. (in press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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