難治性心不全を克服するバイオニック自律神経制御システムの基盤研究

2013 Fiscal Year Annual Research Report

• Project/Area Number: 23220013
• Research Institution: Kyushu University
• Principal Investigator: 砂川 賢二 九州大学, 医学(系)研究科(研究院), 教授 (50163043)
• Co-Investigator(Kenkyū-buntansha): 岸 拓弥 九州大学, 医学(系)研究科(研究院), 講師 (70423514) ; 廣岡 良隆 九州大学, 医学(系)研究科(研究院), 教授 (90284497) ; 井手 友美 九州大学, 医学(系)研究科(研究院), 講師 (90380625)
• Project Period (FY): 2011-05-31 – 2016-03-31
• Keywords: 自律神経制御 / 循環制御 / 心不全 / バイオニック

Research Abstract

２年次までの研究成果を受け、H２６年度はバイオニック自律神経制御システムの要素技術開発を継続するとともに、圧反射機能の低下がどの程度の容量耐性の低下をもたらすのか、慢性実験で確認した。●バイオニック自律神経制御システム開発：動物でバイオニックシステムの長期にわたる治療効果を評価するためには、小型の植え込み型デバイス開発が不可欠になる。実験動物の体重の1/10以下の重量（30g以下）にすることを目標にデバイスを設計し要素技術を確立した。制御部は複雑かつ柔軟な負帰還制御ができるように、畳み込み積分が可能な仕様にした。電源は電池とし当初の目標を超える６週間以上の寿命を実現した。●圧反射が喪失することによる容量耐性低下の慢性動物での検証：圧反射機能の低下が容量耐性に及ぼす影響を慢性動物で評価する。ラットの両側の圧反射救心路（頸動脈洞神経、大動脈弓神経）を除神経した。手術の侵襲から回復した後、覚醒状態で動脈圧、左心房圧をテレメトリで記録した。通常塩分食および高塩分食のもとで、容量耐性がどの様に変化するか対象群と比較した。その結果、除神経では血圧の平均値は変化しないが、その変動が極端に大きくなること、また左房圧の変動も大きくなることが示された。髙塩分負荷では左房圧は20mmHgを超えるようになり、圧反射不全だけで肺水腫の危険にさらされることが明らかになった。これらの実験をもとに、バイオニック自律神経制御システムに必要な制御レンジを確定し、刺激部ならびに制御部の設計に供した。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

●頸動脈洞圧を自在に制御するための、高速サーボポンプの設計開発：圧反射の動特性を明らかにするために、圧受容器に広帯域の圧変動を入力するサーボポンプが不可欠である。従来の経験を集約した結果、遮断周波数は１００Hzに達する超高速サーボポンプが完成した。予定以上の開発成果である。●バイオニック圧反射システムの制御アルゴリズム、システム設計：バイオニック圧反射システムは動脈圧を感知し、圧受容器求心路を電子的に刺激することで圧反射を再構成する。すでに仕様を満たす実時間動作システムが完成しており予定以上の開発成果と考えている。●心不全のモデル動物作成：心不全には収縮機能が低下した心不全と収縮機能が保持された心不全がある。とりわけ収縮機能保持型の心不全はモデル動物の作成が容易でない。この問題は高血圧発症ラットが心肥大は起こすが収縮機能は低下しない時期があることが明らかになり、解決した。●動脈圧反射障害を再現する心不全モデル動物作成：圧反射障害を有する慢性動物のモデル作成は容易でない。本研究では第一段階では圧受容器求心路をすべて切断することでその目的を到達した。しかしながら、最終的には求心路の保存が必須である。現在機械的に減圧する方法で圧反射機能を低下させる戦略をとっている。大動物ではできており、小動物に対しても充分に可能と考えている。●病態モデルに対するバイオニック圧反射システムの有効性の検証：試作されたバイオニック圧反射システムが想定した機能を発揮するかどうか急性期実験で証明されている。中長期的な効果に関しては今後の最大の課題であるが、全体としては予定以上の成果が見込まれるものと考えている。

Strategy for Future Research Activity

３年次までの研究成果を受け、平成２７年度はこれまで開発してきた技術を統合し植込型（および非植込型）のバイオニック自律神経制御システムを開発する。開発されたバイオニック圧反射システムを駆使して収縮機能保持型および低下型心不全の両者に対して最適治療条件を探索する。●バイオニック圧反射システムの開発：制御器や神経刺激ユニットなどの心臓部は完成しているが、圧センサーとの接続が残っている。既存の圧センサーを用いることで実用化は可能である。圧センサーは血管内留置型と血管外歪み検出型の両者を比較検討する。また、植え込みシステムのバックアップとして、非植込型（体外型）のバイオニック圧反射システムを平行して開発する。●収縮機能保持型心不全のバイオニック治療戦略の確立：高血圧発症ラットの片側の圧受容器を還流する動脈を結紮することで減圧し、持続的な高血圧を作成する。心エコーで心肥大が起き、かつ心機能が保持される時期を確定する。バイオニック圧反射システムの制御条件を網羅的に変え、血圧や心拍のばらつき、肺欝血、心不全、心肥大、心筋組織、その他のサイトカインを含む神経内分泌系活性化を定量する。これらの結果を基にバイオニック圧反射システムの最適治療条件を探索する。●収縮機能低下型心不全のバイオニック治療戦略の確立：上記と同様にラットで持続的な高血圧を作成する。心エコーで心肥大が起き、かつ心収縮機能が低下する時期を確定する。バイオニック圧反射システムの制御条件を網羅的に変え、血圧や心拍のばらつき、肺欝血、心不全、心肥大、心筋組織、その他のサイトカインを含む神経内分泌系活性化を定量する。これらの結果を基にバイオニック圧反射システムの最適治療条件を探索する。収縮機能が容易に低下しない場合には心筋梗塞を作成し心機能の悪化を加速させる。

Research Products

• [Journal Article] Benefit of azilsartan on blood pressure elevation around rest-to-active phase in spontaneously hypertensive rats. (2014)
  • Author(s): Isegawa K, Hirooka Y, Kishi T, Yasukawa K, Utsumi H, Sunagawa K.
  • Journal Title: Clin Exp Hypertens. Volume: 37 Pages: 45-50
  • DOI: 10.3109/10641963.2014.897721.
  • Peer Reviewed
• [Journal Article] Corticosterone-activated mineralocorticoid receptor contributes to salt-induced sympathoexcitation in pressure overload mice. (2014)
  • Author(s): Ito K, Hirooka Y, Sunagawa K.
  • Journal Title: Clin Exp Hypertens. Volume: 36 Pages: 550-556
  • DOI: 10.3109/10641963.2014.881841.
  • Peer Reviewed
• [Journal Article] Central neuregulin-1/ErbB signaling modulates cardiac function via sympathetic activity in pressure overload-induced heart failure (2014)
  • Author(s): Matsukawa R, Hirooka Y, Ito K, Honda N, Sunagawa K.
  • Journal Title: J Hypertens. Volume: 32 Pages: 817-825
  • DOI: 10.1097/HJH.0000000000000072.
  • Peer Reviewed
• [Journal Article] Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function. (2014)
  • Author(s): Funakoshi K, Hosokawa K, Kishi T, Ide T, Sunagawa K.
  • Journal Title: J Card Fail. Volume: 20 Pages: 53-59
  • DOI: 10.1016/j.cardfail.2013.11.007.
  • Peer Reviewed
• [Journal Article] Telmisartan reduces mortality and left ventricular hypertrophy with sympathoinhibition in rats with hypertension and heart failure. (2014)
  • Author(s): Kishi T, Hirooka Y, Sunagawa K.
  • Journal Title: Am J Hypertens. Volume: 27 Pages: 260-267
  • DOI: 10.1093/ajh/hpt188.
  • Peer Reviewed
• [Journal Article] Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice. (2014)
  • Author(s): Hashimoto T, Ichiki T, Watanabe A, Hurt-Camejo E, Michaëlsson E, Ikeda J, Inoue E, Matsuura H, Tokunou T, Kitamoto S, Sunagawa K.
  • Journal Title: Vascul Pharmacol Volume: In press Pages: Ｓ1537-1891
  • DOI: 10.1016/j.vph.2014.03.006.
  • Peer Reviewed
• [Journal Article] Combining irbesartan and trichlormethiazide enhances blood pressure reduction via inhibition of sympathetic activity without adverse effects on metabolism in hypertensive rats with metabolic syndrome. (2014)
  • Author(s): Nishihara M, Hirooka Y, Sunagawa K.
  • Journal Title: Clin Exp Hypertens Volume: In press Pages: In press
  • Peer Reviewed
• [Journal Article] Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. (2014)
  • Author(s): Katsuki S, Matoba T, Nakashiro S, Sato K, Koga J, Nakano K, Nakano Y, Egusa S, Sunagawa K, Egashira K.
  • Journal Title: Circulation. Volume: 129 Pages: 896-906
  • DOI: 10.1161/CIRCULATIONAHA.113.002870.
  • Peer Reviewed
• [Journal Article] Suppression of abdominal aortic aneurysm formation by inhibition of prolyl hydroxylase domain protein through attenuation of inflammation and extracellular matrix disruption. (2014)
  • Author(s): Watanabe A, Ichiki T, Sankoda C, Takahara Y, Ikeda J, Inoue E, Tokunou T, Kitamoto S, Sunagawa K.
  • Journal Title: Clin Sci Volume: 126 Pages: 671-678
  • DOI: 10.1042/CS20130435.
  • Peer Reviewed
• [Journal Article] Potential clinical application of recently discovered brain mechanisms involved in hypertension. (2013)
  • Author(s): Hirooka Y, Kishi T, Ito K, Sunagawa K.
  • Journal Title: Hypertension. Volume: 62 Pages: 995-1002
  • DOI: 10.1161/HYPERTENSIONAHA.113.00801.
  • Peer Reviewed
• [Journal Article] Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure. (2013)
  • Author(s): Honda N, Hirooka Y, Ito K, Matsukawa R, Shinohara K, Kishi T, Yasukawa K, Utsumi H, Sunagawa K.
  • Journal Title: J Hypertens Volume: 31 Pages: 2300-2308
  • DOI: 10.1097/HJH.0b013e328364a2a1.
  • Peer Reviewed
• [Journal Article] Cardiac phase-targeted dynamic load on left ventricle differentially regulates phase-sensitive gene expressions and pathway activation (2013)
  • Author(s): Onitsuka K, Ide T, Arai S, Hata Y, Murayama Y, Hosokawa K, Sakamoto T, Tobushi T, Sakamoto K, Fujino T, Sunagawa K.
  • Journal Title: J Mol Cell Cardiol. Volume: 64 Pages: 30-38
  • DOI: 10.1016/j.yjmcc.2013.08.008.
  • Peer Reviewed
• [Journal Article] Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure. (2013)
  • Author(s): Ogawa K, Hirooka Y, Kishi T, Ide T, Sunagawa K.
  • Journal Title: PLoS One Volume: 8 Pages: e69053
  • DOI: 10.1371/journal.pone.0069053.
  • Peer Reviewed
• [Journal Article] The overexpression of Twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice. (2013)
  • Author(s): Tanaka A, Ide T, Fujino T, Onitsuka K, Ikeda M, Takehara T, Hata Y, Ylikallio E, Tyynismaa H, Suomalainen A, Sunagawa K.
  • Journal Title: PLoS One. Volume: 8 Pages: e67642
  • DOI: 10.1371/journal.pone.0067642.
  • Peer Reviewed
• [Journal Article] Deletion of phd2 in myeloid lineage attenuates hypertensive cardiovascular remodeling. (2013)
  • Author(s): Ikeda J, Ichiki T, Matsuura H, Inoue E, Kishimoto J, Watanabe A, Sankoda C, Kitamoto S, Tokunou T, Takeda K, Fong GH, Sunagawa K.
  • Journal Title: J Am Heart Assoc. Volume: 2 Pages: e000178
  • DOI: 10.1161/JAHA.113.000178.
  • Peer Reviewed
• [Journal Article] Chitinase inhibition promotes atherosclerosis in hyperlipidemic mice. (2013)
  • Author(s): Kitamoto S, Egashira K, Ichiki T, Han X, McCurdy S, Sakuda S, Sunagawa K, Boisvert WA.
  • Journal Title: Am J Pathol. Volume: 183 Pages: 313-325
  • DOI: 10.1016/j.ajpath.2013.04.003.
  • Peer Reviewed
• [Journal Article] Prolyl hydroxylase domain protein 2 plays a critical role in diet-induced obesity and glucose intolerance. (2013)
  • Author(s): Matsuura H, Ichiki T, Inoue E, Nomura M, Miyazaki R, Hashimoto T, Ikeda J, Takayanagi R, Fong GH, Sunagawa K.
  • Journal Title: Circulation Volume: 127 Pages: 2078-2087
  • DOI: 10.1161/CIRCULATIONAHA.113.001742.
  • Peer Reviewed
• [Journal Article] Brain sigma-1 receptor stimulation improves mental disorder and cardiac function in mice with myocardial infarction. (2013)
  • Author(s): Ito K, Hirooka Y, Sunagawa K.
  • Journal Title: J Cardiovasc Pharmacol. Volume: 62 Pages: 222-228
  • DOI: 10.1097/FJC.0b013e3182970b15.
  • Peer Reviewed
• [Journal Article] Inhibition of neuregulin-1/ErbB signaling in the rostral ventrolateral medulla leads to hypertension through reduced nitric oxide synthesis. (2013)
  • Author(s): Matsukawa R, Hirooka Y, Ito K, Sunagawa K.
  • Journal Title: Am J Hypertens Volume: 26 Pages: 51-57
  • DOI: 10.1093/ajh/hps005.
  • Peer Reviewed
• [Journal Article] Role of hypothalamic angiotensin type 1 receptors in pressure overload-induced mineralocorticoid receptor activation and salt-induced sympathoexcitation. (2013)
  • Author(s): Ito K, Hirooka Y, Nakano M, Honda N, Matsukawa R, Sunagawa K.
  • Journal Title: Hypertens Res. Volume: 36 Pages: 513-519
  • DOI: 10.1038/hr.2012.221.
  • Peer Reviewed
• [Journal Article] Pivotal role of Rho-associated kinase 2 in generating the intrinsic circadian rhythm of vascular contractility. (2013)
  • Author(s): Saito T, Hirano M, Ide T, Ichiki T, Koibuchi N, Sunagawa K, Hirano K.
  • Journal Title: Circulation. Volume: 127 Pages: 104-114
  • DOI: 10.1161/CIRCULATIONAHA.112.135608.
  • Peer Reviewed
• [Journal Article] Mineralocorticoid receptors/epithelial Na(+) channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats. (2013)
  • Author(s): Nakano M, Hirooka Y, Matsukawa R, Ito K, Sunagawa K.
  • Journal Title: Hypertens Res. Volume: 36 Pages: 277-284
  • DOI: 10.1038/hr.2012.174.
  • Peer Reviewed
• [Presentation] Central Sympathoinhibition by Moxonidine Attenuated Brain Oxidative Stress, Prevented Cardiac Dysfunction and Improved Prognosis in Rats With Hypertensive Heart Failure. (2013)
  • Author(s): Honda N, Hirooka Y, Ito K, Matsukawa R, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Changes in the Vascular Properties, Not the Ventricular Properties, Predominantly Contributes to the Baroreflex Induced Arterial Pressure Regulation. (2013)
  • Author(s): Sakamoto T, Kakino T, Saku K, Sakamoto K, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Salt Loading in the Presesnce of Baroreflex Failure Predisposes to Pulmonary Edema in Spontaneously Hypertensive Rat. (2013)
  • Author(s): Saku K, Sakamoto K, Kakino T, Oga Y, Nishizaki A, Ikeda M, Kuwahara Y, Kishi T, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Concomitant Vagal Nerve Stimulation With Total Flow Support of Left Ventricular Assist Device Virtually Nullifies the Infarct Size in Ischemia Reperfusion Model. (2013)
  • Author(s): Saku K, Kakino T, Akashi T, Sakamoto K, Sakamoto T, Ide T, Kishi T, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Total Left Ventricular Unloading Strikingly Reduces the Infarct Size in Ischemia Reperfusion. (2013)
  • Author(s): Kakino T, Saku K, Akashi T, Sakamoto K, Sakamoto T, Kishi T, Ide T, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Crucial Role of Proteinase-Activated Receptor 1 in the Development of Monocrotaline Induced Pulmonary Arterial Hypertension in Rats. (2013)
  • Author(s): Kuwabara Y, Abe K, Hirano M, Hirooka Y, Sunagawa K, Hirano K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] A Novel Endothelin Receptor Antagonist, Macitentan Markedly Improved Severe Pulmonary Arterial Hypertension in Rats by a Nearly Complete Blockade of Endothelin Receptors. (2013)
  • Author(s): Kunita M, Abe K, Hirooka Y, Kuwabara Y, Hirano K, Oka M, Sunagawa K.
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, U.S.A
  • Year and Date: 20131116-20131120
• [Presentation] Beneficial impact of vagal nerve stimulation on CHF is not stimulus dose dependent. (2013)
  • Author(s): Nishizaki A, Sakamoto K, Saku K, Ikeda M, Kakino T, Oga Y, Kuwabara Y, Kishi T, Ide T, Sunagawa K.
  • Organizer: 24th International Sumposium on the Autonomic Nervous System 2013.
  • Place of Presentation: The Big Island, Hawaii
  • Year and Date: 20131023-20131026
• [Presentation] Volume loading evokes biphasic changes in sympathetic nerve activity via vagally mediated low pressure baroreflex. (2013)
  • Author(s): Oga Y, Kishi T, Saku K, Kakino T, Ikeda M, Nishizaki A, Kuwabara Y, Ide T, Sunagawa K.
  • Organizer: 24th International Sumposium on the Autonomic Nervous System 2013.
  • Place of Presentation: The Big Island, Hawaii
  • Year and Date: 20131023-20131026
• [Presentation] Afferent vagal nerve stimulation resets the baroreflex neural arc and inhibits sympathetic nerve activity. (2013)
  • Author(s): Saku K, Sakamoto K, Oga Y, Nishizaki A, Kishi T, Ide T, Sunagawa K.
  • Organizer: 24th International Sumposium on the Autonomic Nervous System 2013.
  • Place of Presentation: The Big Island, Hawaii
  • Year and Date: 20131023-20131026
• [Presentation] Quantitative synthesis of baroreflex on dynamic circulatory equilibrium: model based analysis and experimental validation. (2013)
  • Author(s): Sakamoto T, Sunagawa K.
  • Organizer: 24th International Sumposium on the Autonomic Nervous System 2013.
  • Place of Presentation: The Big Island, Hawaii
  • Year and Date: 20131023-20131026
• [Presentation] Total unloading of the Left Ventricle by circulatory Assist Device (LVAD) strikingly reduces the infract size in ischemia-reperfusion injury. (2013)
  • Author(s): Saku K, Kakino T, Sakamoto K, Sakamoto T, Akashi T, Hata Y, Kishi T, Ide T, Sunagawa K.
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 20130831-20130904
• [Presentation] Afferent vagal nerve stimulation induced sympathoinhibition may in part attribute to the beneficial impact of vagal nerve stimulation on heart failure. (2013)
  • Author(s): Saku K, Sakamoto K, Onitsuka K, Tobushi T, Oga Y, Nishizaki A, Kakino T, Kishi T, Ide T, Sunagawa K.
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 20130831-20130904
• [Presentation] Prediction of hemodynamic impact of the venoarterial Extracorporeal Membrane Oxygenation (ECMO) (2013)
  • Author(s): Kakino T, Sakamoto K, Saku K, Sakamoto T, Akashi T, Oga Y, Nishizaki A, Kishi T, Ide T, Sunagawa K.
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 20130831-20130904
• [Presentation] Central Sympathoinhibition by Moxonidine Improves Prognosis in Rats with Hypertensive Heart Failure. (2013)
  • Author(s): Honda N, Hirooka Y, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] The Increase of Mitochondrial DNA Copy Number Attenuates Eccentric Cardiac Remodeling in Volume Overload Model. (2013)
  • Author(s): Ikeda M, Ide T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Ideal Depressor Effect of New Angiotensin II Receptor Blocker, Azilsartan, Around Rest-To-Active Phase in Hypertensive Rats. (2013)
  • Author(s): Isegawa K, Hirooka Y, Kishi T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Full Support Left Ventricular Assist Device (LVAD) Remarkably Reduces the Infarct Size in Ischemia Reperfusion Model in Dogs. (2013)
  • Author(s): Kakino T, Saku K, Sakamoto K, Sakamoto T, Kishi T, Ide T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Splenic Regulatory T Cells Were Associated with AT1 Receptors in the Brain in Hypertensive Rats. (2013)
  • Author(s): Katsuki M, Hirooka Y, Kishi T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] A New Endothelin Receptor Antagonist Macitentan Prevents Endothelin-1 Induced Contraction in Intrapulmonary Arteries in Rats with Severe Pulmonary Arterial Hypertension. (2013)
  • Author(s): Kunita M, Abbe K, Hirooka Y, Hirano K, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] High Voltage, Not Age and Blood Pressure, of Stimulus Exaggerates Inducibility of Atrial Fibrillation by Rapid Electrical Stimulation in Hypertensive Rats. (2013)
  • Author(s): Nagayama T, Kishi T, Hirooka Y, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Vascular Intrinsic Circadian Rhythm of Vascular Contractility under the Regulation of Clock Gene RORa. (2013)
  • Author(s): Saito T, Ide T, Ichiki T, Sunagawa K, Hirano K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Prediction of Hemodynamic Impact of the Venoarterial Extracorporeal Membrane Oxygenation (ECMO). (2013)
  • Author(s): Sakamoto K, Kakino T, Saku K, Tanaka A, Sakamoto T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Baroreflex Induced Changes in Stressed Blood Volume Is the Central Mechanism Preventing Volume Load Induced Pulmonary Edema. (2013)
  • Author(s): Sakamoto T, Kakino T, Sakamoto K, Saku K, Sunagawa K
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Concomitant Vagal Stimulation on Top of Left Ventricular Assist Device Markedly Reduces the Infarct Size in Ischemia Reperfusion Model. (2013)
  • Author(s): Saku K, Kakino T, Sakamoto K, Kishi T, Ide T, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Closed-Loop Neuromodulation Integrated into the Native Physiology Saves Many Patients with Refractory Cardiovascular Diseases. (2013)
  • Author(s): Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] Baroreflex Steepens the Renal Pressure-Diuresis Relation and Contributes to Stabilize Body Fluid Equilibrium. (2013)
  • Author(s): Tobushi T, Kishi T, Hosokawa K, Murayama Y, Sunagawa K.
  • Organizer: 35th Annual International Conference of the IEEE Engineering in Medicine & Biology Society 2013
  • Place of Presentation: Osaka, Japan
  • Year and Date: 20130704-20130707
• [Presentation] The Increase of Mitochondrial DNA Copy Number Attenuates Eccentric Cardiac Remodeling In Volume Overload Model. (2013)
  • Author(s): Ikeda M, Ide T, Fujino T, Hata Y, Takehara T, Onitsuka K, Tobushi T, Sakamoto K, Saku K, Kakino T, Tyynismaa H, Suomalainen A, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424
• [Presentation] Central Sympathoinhibition Ameliorates the Reduction of Splenic Regulatory T Cells with Decreased IL-17 Production in Hypertensive Rats (2013)
  • Author(s): Katsuki M, Hirooka Y, Kishi T, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424
• [Presentation] Azilsartan, New Angiotensin II Type 1 Receptor Blocker, Would Suppress Morning Surge in Hypertension. (2013)
  • Author(s): Isegawa K, Hirooka Y, Kishi T, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424
• [Presentation] Quantitative Prediction of Impact of Left Ventricular Assist Device (LVAD) on Hemodynamics. (2013)
  • Author(s): Kakino T, Saku K, Sakamoto T, Sakamoto K, Akashi T, Tobushi T, Murayama Y, Fujino T, Onitsuka K, Ikeda M, Oga Y, Nishizaki A, Kuwabara Y, Ide T, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424
• [Presentation] Central sympathoinhibition by moxonidine attenuates brain oxidative stress, prevents cardiac remodeling and improves prognosis associated with reduction of sympathetic hyperactivity in rats with hypertensive heart failure. (2013)
  • Author(s): Honda N, Hirooka Y, Matsukawa R, Ito K, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424
• [Presentation] Afferent Vagal Nerve Stimulation Resets the Baroreflex Neural Arc and Inhibits Sympathetic Nerve Activity. (2013)
  • Author(s): Saku K, Sakamoto K, Hosokawa K, Kakino T, Ikeda M, Oga Y, Nishizaki A, Ide T, Sunagawa K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, U.S.A.
  • Year and Date: 20130420-20130424