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2009 Fiscal Year Annual Research Report

脊髄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  Kyushu University, 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)。さらに血圧応答の動的な特性も明らかになり、バイオニック血圧制御に不可欠な生体応答のモデル化ができた。そのモデルをもとに実用機の一次プロトタイプを試作した。プロトタイプを用いた臨床試験により、頚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。最終年度は長時間の安定した動作、システムの安全性等、実用化に必要な更なる開発を行う予定である。

  • Research Products

    (42 results)

All 2010 2009

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (17 results)

  • [Journal Article] Angiotensin II type 1 receptor-activated caspase-3 throughras/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 55

      Pages: 291-297

    • 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. 55

      Pages: 184-190

    • 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. 33

      Pages: e4-e7

    • Peer Reviewed
  • [Journal Article] Atorvastatin improves the impaired baroreflex sensitivity via anti-oxidant effect in the rostral ventrolateral medulla of SHRSP.2009

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

      Clin Exp Hypertens. 31

      Pages: 698-704

    • Peer Reviewed
  • [Journal Article] Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method.2009

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

      Hypertens Res. 32

      Pages: 1091-1096

    • Peer Reviewed
  • [Journal Article] Inhibition of prolyl hydroxylase domain-containing protein suppressed lipopolysaccharide-induced TNF-alpha expression.2009

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

      Arterioscler Thromb Vasc Biol. 29

      Pages: 2132-2137

    • Peer Reviewed
  • [Journal Article] Coronary aneurysm associated with coronary perforation after sirolimus-eluting stents implantation : Close follow-up exceeding 2 years by coronary 3-dimensional computed tomography.2009

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

      J Cardiol. 54

      Pages: 115-120

    • Peer Reviewed
  • [Journal Article] Bundle branch re-entry ventricular tachycardia in a patient with myotonic dystrophy.2009

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

      J Cardiol. 53

      Pages: 463-466

    • Peer Reviewed
  • [Journal Article] Atorvastatin might improve ventricular electrostability and decelerate the deterioration of renal function in patients with heart failure and diabetes mellitus.2009

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

      J Cardiol. 53

      Pages: 341-348

    • Peer Reviewed
  • [Journal Article] Formulation of nanoparticle-eluting stents by a cationic electrodeposition coating technology : efficient nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries.2009

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

      JACC Cardiovasc Interv. 2

      Pages: 277-283

    • Peer Reviewed
  • [Journal Article] Improvement of neovascularization capacity of bone marrow mononuclear cells from diabetic mice by ex vivo pretreatment with resveratrol.2009

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

      Hypertens Res. 32

      Pages: 542-547

    • Peer Reviewed
  • [Journal Article] Role of inducible nitric oxide synthase in rostral ventrolateral medulla in blood pressure regulation in spontaneously hypertensive rats.2009

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

      Clin Exp Hypertens. 31

      Pages: 281-286

    • Peer Reviewed
  • [Journal Article] Cilnidipine inhibits the sympathetic nerve activity and improves baroreflex sensitivity in patients with hypertension.2009

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

      Clin Exp Hypertens. 31

      Pages: 241-249

    • Peer Reviewed
  • [Journal Article] Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis.2009

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

      Hypertens Res. 32

      Pages: 466-471

    • Peer Reviewed
  • [Journal Article] Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium.2009

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

      Arterioscler Thromb Vasc Biol. 29

      Pages: 796-801

    • Peer Reviewed
  • [Journal Article] Nanoparticle-mediated delivery of nuclear factor kappaB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension.2009

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

      Hypertension. 53

      Pages: 877-883

    • Peer Reviewed
  • [Journal Article] Acquisition of brain Na sensitivity contributes to salt-induced sympathoexcitation and cardiac dysfunction in mice with pressure overload.2009

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

      Circ Res. 104

      Pages: 1004-1011

    • Peer Reviewed
  • [Journal Article] Servo-controlled hind-limb electrical stimulation for short-term arterial pressure control.2009

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

      Circ J. 73

      Pages: 851-859

    • Peer Reviewed
  • [Journal Article] Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta.2009

    • Author(s)
      Tian Q, et al
    • Journal Title

      Hypertension. 53

      Pages: 798-804

    • Peer Reviewed
  • [Journal Article] Chest pain without significant coronary stenosis after implantation of sirolimus-eluting stents.2009

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

      Intern Med. 48

      Pages: 213-217

    • Peer Reviewed
  • [Journal Article] Soluble Flt-1 gene transfer ameliorates neointima formation after wire injury in flt-1 tyrosine kinase-deficient mice.2009

    • Author(s)
      Koga J, et al
    • Journal Title

      Arterioscler Thromb Vase Biol. 29

      Pages: 458-464

    • Peer Reviewed
  • [Journal Article] Intracardiac echocardiography-guided cardiac tumor biopsy.2009

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

      Circ J 73

      Pages: 381-383

    • Peer Reviewed
  • [Journal Article] Time-dependent changes of myocardial and systemic oxidative stress are dissociated after myocardial infarction.2009

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

      Free Radic Res. 43

      Pages: 37-46

    • Peer Reviewed
  • [Journal Article] Computationally managed bradycardia improved cardiac energetics while restoring normal hemodynamics in heart failure.2009

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

      Ann Biomed Eng. 37

      Pages: 82-93

    • Peer Reviewed
  • [Journal Article] Wavelet-based system identification of short-term dynamic characteristics of arterial baroreflex.2009

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

      Ann Biomed Eng. 37

      Pages: 112-128

    • Peer Reviewed
  • [Presentation] Vagal Nerve Stimulation during Ischemia-Reperfusion(I/R)Reduces the Infarct Size and Ameliorates Subsequent Left Ventricular(LV)Dysfunction/Remodeling2010

    • Author(s)
      Ando M, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-07
  • [Presentation] Arterial Pressure Destabilization in Patients with Cervical Spinal Cord Injury Requires Tailored Therapeutic Strategies Depending upon the Post Injury Period2010

    • Author(s)
      Sakamoto T, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-07
  • [Presentation] Decreases in Brain Sigma-1 Receptor Contribute to Sympathetic Hyperactivation in Mice with Heart Failure.2010

    • Author(s)
      Ito K, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-07
  • [Presentation] Telmisartan Improves Endothelial Function and Decreases Sympathetic Nerve Activity to a Greater Extent than Candesartan in Patients with Metabolic Syndrome2010

    • Author(s)
      Kishi T, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-07
  • [Presentation] Apoptosis of Astrocyte Mediated by Toll-like Receptor 4 and Apoptosis Signal-Regulating 1 in Cardiovascular Center Causes Sympathoexcitation in Hypertensive Rats2010

    • Author(s)
      Kishi T, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-07
  • [Presentation] Electrical Afferent Vagal Stimulation Markedly Inhibits Sympathetic Nervous Activity Irrespective of Baroreflex Activation without Lowering Blood Pressure.2010

    • Author(s)
      Hosokawa K, et al.
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-06
  • [Presentation] Sildenafil Improves Exercise Tolerance in Patients with Refractory Heart Failure through Ameliorating Right Ventricular Afterload Mismatch2010

    • Author(s)
      Sakamoto T, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-06
  • [Presentation] AT1 Receptor-activated Ras-induced Apoptosis and P53-induced Senescence in the Cardiovascular Center of Brainstem Contributes to Sympathoexcitaion of Hypertensive Rats.2010

    • Author(s)
      Kishi T, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-06
  • [Presentation] Neuregulin-1/erbB Signaling in the Rostral Ventrolateral Medulla(RVLM)of Brainstem Contributes to Neural Regulation of Blood Pressure.2010

    • Author(s)
      Matsukawa R, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-06
  • [Presentation] Reduction of ErbB receptors in the Brainstem Contributes to Neural Mechanisms of Hypertension.2010

    • Author(s)
      Matsukawa R, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-05
  • [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, et al
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-05
  • [Presentation] Left Ventricular Hypertrophy Enhances the Expression of Mineralocorticoid Receptor and Epithelial Na Channels in the Brain and Leads to Salt-sensitive Sympathetic Hyperactivation and Left Ventricular Dysfunction.2009

    • Author(s)
      Ito K, et al
    • Organizer
      Scientific Sessions of the American Heart Association
    • Place of Presentation
      Orland
    • Year and Date
      20091100
  • [Presentation] The Reduction of Brain Sigma-1 Receptor Contributes to Sympathetic Hyperactivation in Heart Failure2009

    • Author(s)
      Ito K, et al
    • Organizer
      Scientific Sessions of the American Heart Association
    • Place of Presentation
      Orland
    • Year and Date
      2009-11-18
  • [Presentation] Dysregulation of brain MR-ENaCs pathway contributes to the acquisition of brain Na sensitivity in mice with LVH2009

    • Author(s)
      伊藤浩司, 他
    • Organizer
      第13回日本心不全学会
    • Place of Presentation
      福岡市
    • Year and Date
      2009-10-30
  • [Presentation] エプレレノンは圧負荷モデルにおける脳内Na感受性亢進を抑制することによって食塩負荷に伴う交感神経活性化を軽減し心機能を改善する。-脳内MR-ENaC経路の重要性2009

    • Author(s)
      伊藤浩司, 他
    • Organizer
      第32回日本高血圧学会総会
    • Place of Presentation
      大津市
    • Year and Date
      2009-10-03
  • [Presentation] Bionic autonomic neuromodulation revolutionizes cardiology in the 21st century.2009

    • Author(s)
      Sunagawa K
    • Organizer
      EMBC 2009
    • Place of Presentation
      Minneapolis
    • Year and Date
      2009-09-03
  • [Presentation] Brain salt sensitivity in mice with LVH is enhanced via Rho-kinase pathway through ENaC activation2009

    • Author(s)
      Ito K, et al
    • Organizer
      Experimental Biology 2009
    • Place of Presentation
      New Orleans
    • Year and Date
      2009-04-19

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Published: 2011-06-16   Modified: 2016-04-21  

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