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2010 Fiscal Year Annual Research Report

脊随損傷患者の血圧調節失調を克服するためのバイオニック血圧制御システムの開発

Research Project

Project/Area Number 18100006
Research InstitutionKyushu University

Principal Investigator

砂川 賢二  九州大学, 医学研究院, 教授 (50163043)

Co-Investigator(Kenkyū-buntansha) 廣岡 良隆  九州大学, 大学病院, 講師 (90284497)
樗木 晶子  九州大学, 医学研究院, 教授 (60216497)
戸高 浩司  九州大学, 大学病院, 講師 (40398061)
Keywordsバイオニック医学 / 血圧制御 / 脊髄損傷 / 自動治療 / 生体医工学
Research Abstract

【背景・目的】頚髄損傷患者は交感神経遠心路の障害により、深刻な体位性低血圧に苛まれる。そのため受動的な頭位の挙上も低血圧のため制限されQOLは劣悪である。申請者は自律神経系に工学的な手法で介入し、制御理論を駆使して循環を制御するバイオニック心臓病学の基礎研究で多くの実績をあげてきた。
本研究は従来の研究成果を元に、頚髄損傷患者の体位性低血圧を非侵襲的に防止するバイオニック血圧制御システムの開発を目指す。【進捗状況】動物実験では瞬時血圧を負帰還しながら交感神経を腹腔神経叢あるいは脊髄硬膜外電極で刺激することで、血圧を制御することができることを示してきた。しかしながら、臨床応用には、さらなる低侵襲化が必須である。そのため、平成18-19年度は体性入力を利用した皮膚の電気刺激による脊髄反射を介した交感神経の活性化制御の可能性を検討した。その結果、非侵襲な皮膚の電気刺激で血圧を変えることができることが明らかになった。平成20-21年度は皮膚の刺激部位、刺激電流の大きさ、周波数、刺激電極の大きさ等について系統的に検索した。その結果、下腹部を中心に最大応答が得られることが明らかになった(知財国際出願)。H22年度はさらに血圧応答の動的な特性を明らかにすることで、バイオニック血圧制御に不可欠な生体応答のモデル化を行った。さらに、神経の持続刺激は慣れ現象をおこすことが知られていることから、実用化の大きな障害になる慣れ現象を回避する間歇刺激法の最適化を行った。これらの成果を導入したプロトタイプを用いた臨床試験により、脊髄損傷患者の頭位を挙上させて誘発される体位性低血圧を当該システムで防ぐことができることが明らかになった。
この実績により当該事業は先端医療開発特区(平成20-24年度)に選定された。

  • Research Products

    (43 results)

All 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (29 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension2011

    • Author(s)
      Hirooka Y, et al
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol.

      Volume: 300 Pages: R818-R826

    • Peer Reviewed
  • [Journal Article] Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension.2011

    • Author(s)
      Chen L, et al
    • Journal Title

      Hypertension

      Volume: 57 Pages: 343-350

    • Peer Reviewed
  • [Journal Article] A case of multiple focal nodular hyperplasia in the liver which developed after heart transplantation.2011

    • Author(s)
      Fujino T, et al
    • Journal Title

      Intern Med.

      Volume: 50 Pages: 43-46

    • Peer Reviewed
  • [Journal Article] Baroreflex sensitivity might predict responders to milrinone in patients with heart failure.2010

    • Author(s)
      Kishi T, Sunagawa K.
    • Journal Title

      Int Heart J

      Volume: 51 Pages: 411-415

    • Peer Reviewed
  • [Journal Article] Para-Hisian pacing for a pediatric patient with a congenitally corrected transposition of the great arteries (SLL).2010

    • Author(s)
      Takemoto M, et al
    • Journal Title

      Pacing Clin Electrophysiol.

      Volume: 33 Pages: e4-7

    • Peer Reviewed
  • [Journal Article] Sympathoinhibition induced by centrally administered atorvastatin is associated with alteration of NAD(P)H and Mn superoxide dismutase activity in rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats.2010

    • Author(s)
      Kishi T, et al
    • Journal Title

      J Cardiovasc Pharmacol.

      Volume: 55 Pages: 184-190

    • Peer Reviewed
  • [Journal Article] Cross-sectional characterization of all classes of antihypertensives in terms of central blood pressure in Japanese hypertensive patients.2010

    • Author(s)
      Miyashita H, et al
    • Journal Title

      Am J Hypertens

      Volume: 23 Pages: 260-268

    • Peer Reviewed
  • [Journal Article] Angiotensin II type 1 receptor-activated caspase-3 through ras/mitogen-activated protein kinase/extracellular signal-regulated kinase in the rostral ventrolateral medulla is involved in sympathoexcitation in stroke-prone spontaneously hypertensive rats.2010

    • Author(s)
      Kishi T, et al
    • Journal Title

      Hypertension

      Volume: 55 Pages: 291-297

    • Peer Reviewed
  • [Journal Article] Nanoparticle-mediated endothelial cell-selective delivery of pitavastatin induces functional collateral arteries (therapeutic arteriogenesis) in a rabbit model of chronic hind limb ischemia.2010

    • Author(s)
      Oda S, et al
    • Journal Title

      J Vasc Surg.

      Volume: 52 Pages: 412-420

    • Peer Reviewed
  • [Journal Article] Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload.2010

    • Author(s)
      Ito K, Hirooka Y, Sunagawa K
    • Journal Title

      J Hypertens.

      Volume: 28 Pages: 1449-1458

    • Peer Reviewed
  • [Journal Article] Acetylcholinesterase inhibitors attenuate atherogenesis in apolipoprotein E-knockout mice.2010

    • Author(s)
      Inanaga K, et al
    • Journal Title

      Atherosclerosis.

      Volume: 213 Pages: 52-58

    • Peer Reviewed
  • [Journal Article] Oxidative stress and central cardiovascular regulation.-Pathogenesis of hypertension and therapeutic aspects.2010

    • Author(s)
      Hirooka Y, et al
    • Journal Title

      Circ J

      Volume: 74 Pages: 827-835

    • Peer Reviewed
  • [Journal Article] Peak Systolic Mitral Annulus Velocity Reflects the Status of Ventricular-Arterial Coupling-Theoretical and Experimental Analyses.

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

      J Am Soc Echocardiogr

      Volume: (In press)

    • Peer Reviewed
  • [Presentation] NPC1L1 Inhibition with Ezetimibe Suppresses Enhanced Formation of Aortic Atherosclerosis Induced by Dietary Cholesterol Oxidation Products in ApoE-deficient Mice2010

    • Author(s)
      Sato K, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-17
  • [Presentation] Nanoparticle-mediated Endothelial Cell-selective Delivery of Pioglitazone Enhances Therapeutic Efficacy of Therapeutic Angiogenesis and Arteriogenesis after Hindlimb Ischemia in Mice2010

    • Author(s)
      Nagahama R, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-16
  • [Presentation] Nanoparticle-Mediated Monocyte-Selective Delivery of Pitavastatin Prevents Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in ApoE-Deficient Mice2010

    • Author(s)
      Katsuki S, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-16
  • [Presentation] AT_1 Receptor-Activated Toll-Like Receptor 4 in the Brainstem Causes Sympathoexcitation in Mice With Heart Failure2010

    • Author(s)
      Ogawa K, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-16
  • [Presentation] Endogenous Angiotensin-(1-7) Activity in the Rostral Ventrolateral Medulla Is Enhanced in Spontaneously Hypertensive Rats via Sympathetic Nerve Activity2010

    • Author(s)
      Nakagaki T, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-16
  • [Presentation] Nanoparticle-Mediated Monocyte-Selective Delivery of Pitavastatin Inhibits Monocyte Activation and Attenuates Plaque Destabilization and Rupture in ApoE-Deficient Mice2010

    • Author(s)
      Katsuki S, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-15
  • [Presentation] Dentification of Rho-associated Kinase 2 (ROCK2) as a Key Molecule Generating the Intrinsic Circadian Rhythm of Vascular Contractility2010

    • Author(s)
      Saito T, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-15
  • [Presentation] Neuregulin-1/ErbB Pathway Modulation of Major Neurotransmitters in the Cardiovascular Center is Crucial for Neural Regulation of Blood Pressure -Possible Involvement of Neuregulin-1/ErbB Pathway in Neural Mechanisms of Hypertension-2010

    • Author(s)
      Matsukawa R, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-15
  • [Presentation] Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension by Modulating Paraventricular Nucleus of Hypothalamus2010

    • Author(s)
      Nishihara M, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-15
  • [Presentation] NPC1L1 Inhibition with Ezetimibe Prevents Accelerated Plaque Destabilization and Rupture Induced by Dietary Cholesterol Oxidation Products in ApoE-deficient Mice2010

    • Author(s)
      Sato K, et al
    • Organizer
      Scientific Sessions 2010, American Heart Association
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      2010-11-14
  • [Presentation] Baroreflex failure makes patients super susceptible to volume overload and predisposes patients to pulmonary edema in the absence of left ventricular systolic failure.2010

    • Author(s)
      Sunagawa K.
    • Organizer
      21^<th> International Symposium on the autonomic nervous system
    • Place of Presentation
      Florida, U.S.A.
    • Year and Date
      2010-11-05
  • [Presentation] Baroreflex regulates arterial pressure by modulating vascular properties, not by modulating ventricular properties.2010

    • Author(s)
      Sunagawa K.
    • Organizer
      21^<th> International Symposium on the autonomic nervous system
    • Place of Presentation
      Florida, U.S.A.
    • Year and Date
      2010-11-05
  • [Presentation] Estimated Venous Return Surface and Cardiac Output Curve Precisely Predicts New Hemodynamics after Volume Change.2010

    • Author(s)
      Sugimachi M, et al
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-03
  • [Presentation] Automated Drug Delivery System for the Management of Hemodynamics and Cardiac Energetic in Acute Heart Failure.2010

    • Author(s)
      Uemura K, et al
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-03
  • [Presentation] Development of Artificial Bionic Baroreflex System2010

    • Author(s)
      Sunagawa K.
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-02
  • [Presentation] How to Quantitatively Synthesize Dynamic Changes in Arterial Pressure from Baroreflexly Modulated Ventricular and Arterial Properties.2010

    • Author(s)
      Sakamoto T, et al
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-02
  • [Presentation] Physiological Significance of Pressure-Volume Relationship : A Load-Independent Index and a Determinant of Pump Function.2010

    • Author(s)
      Sugimachi M, et al
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-02
  • [Presentation] The Pressure-Volume Relationship of the Heart : Past, Present and Future.2010

    • Author(s)
      Sunagawa K.
    • Organizer
      32^<nd> Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2010-09-02
  • [Presentation] Electrical vagal afferent stimulation inhibits sympathetic nervous activity irrespective of baroreflex activation without lowering blood pressure.2010

    • Author(s)
      Hosokawa K, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-28
  • [Presentation] Equilibrium analysis between the venous return surface and cardiac output curve enables us to predict hemodynamic impact of percutaneous cardiopulmonary support.2010

    • Author(s)
      Tanaka A, Sunagawa K
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-28
  • [Presentation] Telmisartan improves cognitive function through the increase in neurotrophic factor and inhibition of apoptosis in hippocampus of rats with metabolic syndrome.2010

    • Author(s)
      Kishi T, Hirooka Y, Sunagawa K.
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-27
  • [Presentation] Intrinsic circadian oscillation of myosin light chain phosphorylation in vascular smooth muscle cells.2010

    • Author(s)
      Saito T, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-27
  • [Presentation] Reduced reactive oxgen species generation in rostral ventrolateral medulla suppresses the pressor response induced by the excitation of the paraventricular nucleus of the hypothalamus in spontaneously hypertensiverats.2010

    • Author(s)
      Nishihara M, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-27
  • [Presentation] Quantitative synthesis of dynamic baroreflex pressure regulation using baroreflex induced changes in ventricular and vascular properties.2010

    • Author(s)
      Sakamoto T, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Presentation] Telmisartan inhibits sympathetic nerve activity through the reduction of oxidative stress and release of GABA in RVLM of hypertensive rats.2010

    • Author(s)
      Kishi T, Hirooka Y, Sunagawa K.
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Presentation] Angiotensin (1-7) into rostral ventrolateral medulla is enhances in spontaneously hypertensive rats.2010

    • Author(s)
      Nakagaki T, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Presentation] Neuregulin-1/erbB signaling in rostral ventrolateral medulla of brainstem is involves in blood pressure regulation alteration of major neurotransmitters.2010

    • Author(s)
      Matsukawa R, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Presentation] Apoptosis of astrocyte mediated by Toll-like receptor 4 and apoptosis signal-regulating 1 in cardiovascular center causes excessive sympathoexcitation in hypertensive rats.2010

    • Author(s)
      Kishi T, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Presentation] Toll-like receptor expression is increased via activation of AT1 receptor in the brain associated with sympathoexcitation in mice with heart failure.2010

    • Author(s)
      Ogawa K, et al
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim, U.S.A.
    • Year and Date
      2010-04-26
  • [Patent(Industrial Property Rights)] Bionic baroreflex system to treat heart failure with preserved ejection fraction2010

    • Inventor(s)
      Sunagawa K, et al
    • Industrial Property Rights Holder
      九州大学
    • Industrial Property Number
      米国特許出願番号:61/384828
    • Filing Date
      2010-09-21
    • Overseas

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Published: 2012-07-19  

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