Innovation of treatment for malignant hyperthermia and arrhythmia by inhibition of abnormal intracellular Ca2+ release through the ryanodine receptor

• Project/Area Number: 20591805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Yamaguchi University
• Principal Investigator: KOBAYASHI Shigeki Yamaguchi University, 医学部附属病院, 助教 (90397993)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Takeshi 山口大学, 大学院・医学系研究科, 助教 (50363122) ; YANO Masafumi 山口大学, 医学部付属病院, 講師 (90294628)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 悪性高熱症 / 心室頻拍症 / 心不全 / ダントロレン / リアノジン受容体 / 不整脈

Research Abstract

Dantrolene, a specific drug for the treatment of malignant hyperthermia, was found to inhibit Ca^<2+> leak through not only the skeletal ryanodine receptor (RyR1), but also the cardiac ryanodine receptor (RyR2) by correcting the defective inter-domain interaction between N-terminal(1-619 amino acid) amd central (2000-2500 amino acid) domains of RyRs. Here, we examined 1)the effect of dantrolene on the Ca2+ release and cardiomyocyte function in chronic rapid pacing-induced heart failure dog model 2) the anti-arrhythmic effect of dantrolene in human CPVT-associated RyR2^<R2474S /+> knock-in (KI) mouse model. In heart failure model, dantrolene corrects defective inter-domain interactions within RyR2 in failing hearts, inhibits spontaneous Ca^<2+> leak, in turn improves cardiomyocyte function in failing hearts. In human CPVT-associated RyR2^<R2474S /+> knock-in (KI) mouse model, dantrolene prevents CPVT, presumably by correction of catecholamine-induced defective inter-domain interaction within RyR2inhibiting and inhibition of Ca^<2+> leak through RyR2. Thus, dantrolene may have a potential to treat heart failure and lethal arrhythmia, specifically targeting RyR2.

Research Products

• [Journal Article] Urinary8-hydroxy-2'-deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure. (2011)
  • Author(s): Kobayashi S, Susa T, Tanaka T, Wada Y, Okuda S, Doi M, Nao T, Yoshiga Y, Yamada J, Okamura T, Ueyama T, Kawamura S, Yano M, Matsuzaki M.
  • Journal Title: Eur J Heart Fail. 13 Pages: 29-36
  • Peer Reviewed
• [Journal Article] Urinary 8-hydroxy-2'-deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure (2011)
  • Author(s): Shigeki Kobayashi
  • Journal Title: Euro J Heart Fail Volume: 13 Pages: 29-36
  • Peer Reviewed
• [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2 (R2474S/+) knock-in mouse model. (2010)
  • Author(s): Kobayashi S, Yano M, Uchinoumi H, Suetomi T, Susa T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Yamamoto T, Matsuzaki M.
  • Journal Title: Cir J. 74 Pages: 2579-2584
  • NAID: 10027424202
  • Peer Reviewed
• [Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure. (2010)
  • Author(s): Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T, Uchinoumi H, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
  • Journal Title: Cardiovasc Res. 87 Pages: 609-617
  • Peer Reviewed
• [Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction. (2010)
  • Author(s): Xu X, Yano M, Uchinoumi H, Hino A, Suetomi T, Ono M, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ikemoto N, Matsuzaki M.
  • Journal Title: Biochem Biophys Res Commun. 394 Pages: 660-666
  • Peer Reviewed
• [Journal Article] Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor. (2010)
  • Author(s): Uchinoumi H, Yano M, Suetomi T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
  • Journal Title: Cir Res. 81 Pages: 1413-1423
  • Peer Reviewed
• [Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction (2010)
  • Author(s): Xiaojuan Xu
  • Journal Title: Biochem Biophys Res Commun Volume: 394 Pages: 660-666
  • Peer Reviewed
• [Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure (2010)
  • Author(s): Makoto Ono
  • Journal Title: Cardiovasc Res Volume: 87 Pages: 609-617
  • Peer Reviewed
• [Journal Article] Dantrolene, a Therapeutic Agent for Malignant Hyperthermia, Inhibits Catecholaminergic Polymorphic Ventricular Tachycardia in a RyR2R2474S/+ Knock-In Mouse Model (2010)
  • Author(s): Shigeki Kobayashi
  • Journal Title: Circ J Volume: 74 Pages: 2579-2584
  • NAID: 10027424202
  • Peer Reviewed
• [Journal Article] Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor (2010)
  • Author(s): Hitoshi Uchinoumi
  • Journal Title: Circ Res Volume: 106 Pages: 1413-1424
  • Peer Reviewed
• [Journal Article] Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor (2010)
  • Author(s): Hitoshi Uchinoumi
  • Journal Title: Cir Res 81 Pages: 1413-1423
  • Peer Reviewed
• [Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction. (2010)
  • Author(s): Xu X
  • Journal Title: Biochem Biophys Res Commun 394 Pages: 660-666
  • Peer Reviewed
• [Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+release in heart failure. (2010)
  • Author(s): Makoto Ono
  • Journal Title: Cardiovasc Res (in press)
  • Peer Reviewed
• [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the ryanodine receptor. (2009)
  • Author(s): Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, IkemotoN, Matsuzaki M.
  • Journal Title: J Am Coll Cardiol. 53 Pages: 1993-2005
  • Peer Reviewed
• [Journal Article] Role of ryanodine receptor as a Ca(2+) regulatory center in normal and failing hearts. (2009)
  • Author(s): Yano M, Yamamoto T, Kobayashi S, Matsuzaki M.
  • Journal Title: J Cardiol. 53 Pages: 1-7
  • NAID: 10025182309
  • Peer Reviewed
• [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts. (2009)
  • Author(s): Tateishi H, Yano M, Mochizuki M, Suetomi T, Ono M, Xu X, Uchinoumi H, Okuda S, Oda T, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
  • Journal Title: Cardiovasc Res. 81 Pages: 536-545
  • Peer Reviewed
• [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the rvanodine recentor (2009)
  • Author(s): Shigeki Kobayashi
  • Journal Title: J Am Coll Cardiol 53 Pages: 1993-2005
  • Peer Reviewed
• [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+leak in failing hearts. (2009)
  • Author(s): Hiroki Tateishi
  • Journal Title: Cardiovasc Res 81 Pages: 536-545
  • Peer Reviewed
• [Journal Article] Role of ryanodine receptor as a Ca(2+)regulatory center in normal and failing hearts. (2009)
  • Author(s): Masafumi Yano
  • Journal Title: J Cardiol 53 Pages: 1-7
  • NAID: 10025182309
  • Peer Reviewed
• [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing inter-domain interactions within the ryanodine receptor. (2009)
  • Author(s): Shigeki Kobayashi
  • Journal Title: J Am Coll Cardiol 53 Pages: 1993-2005
  • Peer Reviewed
• [Journal Article] Defective Ca2+ cycling as a key pathogenic mechanism of heart failure. (2008)
  • Author(s): Yano M, Yamamoto T, Kobayashi S, Ikeda Y, Matsuzaki M.
  • Journal Title: Circ J. 72 Pages: 22-30
  • NAID: 110006935628
  • Peer Reviewed
• [Journal Article] Identification of target domains of the cardiac ryanodine receptor to correct channel disorder in failing hearts. (2008)
  • Author(s): Yamamoto T, Yano M, Xu X, Uchinoumi H, Tateishi H, Mochizuki M, Oda T, Kobayashi S, Ikemoto N, Matsuzaki M.
  • Journal Title: Circulation. 117 Pages: 762-772
  • Peer Reviewed
• [Journal Article] Identification of target domains of the cardiac ryanodine receptor to correct channel disorder in failing hearts (2008)
  • Author(s): Takeshi Yamamoto
  • Journal Title: Circulation 117 Pages: 762-772
  • Peer Reviewed
• [Presentation] Novel Inter-domain Interaction Within RyR2 as a Common Therapeutic Target by Channel Stabilization in Heart Failure and in Heart Failure and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). (2010)
  • Author(s): Masafumi Yano, Masakazu Fukuda, Akihiro Hino, Takeshi Suetomi, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Masunori Matsuzaki.
  • Organizer: 83rd Scientific Session of American Heart Association.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2010-11-15
• [Presentation] Masunori Matsuzaki Urinary 8-Hydroxy-2'-Deoxyguanosine is a Biomarker for Evaluating the Inflammatory Activity and the Effectiveness to Corticosteroids in Patients with Cardiac Sarcoidosis. (2010)
  • Author(s): Takeo Tanaka, Shigeki Kobayashi, Takehisa Susa, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Jutaro Yamada, Takeshi Ueyama, Takayuki Okamura, Shuji Kawamura, Masafumi Yano
  • Organizer: 83rd Scientific Session of American Heart Association.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2010-11-15
• [Presentation] Increased Affinity of Calmodulin Binding to Cardiac Ryanodine Receptor Corrects the Defective Channel Gating in Failing Hearts. (2010)
  • Author(s): Akihiro Hino, Masafumi Yano, Masakazu Fukuda, Takeshi Suetomi, Makoto Ono, Xiaojuan Xu, Hitoshi Uchinoumi, Takehisa Susa, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Masunori Matsuzaki.
  • Organizer: 83rd Scientific Session of American Heart Association.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2010-11-15
• [Presentation] Correction of Defective Calmodulin Binding to Cardiac Ryanodine Receptor Inhibits Aberrant Ca2+ Release in CPVT-associated Mutation. (2010)
  • Author(s): Masakazu Fukuda, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Xiaojuan Xu, Makoto Ono, Hitoshi Uchinoumi, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Masunori Matsuzaki.
  • Organizer: 83rd Scientific Session of American Heart Association.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2010-11-15
• [Presentation] Mutation-linked Defective Domain Interaction within the Ryanodine Receptor Causes Ca2+ Leak Leading to Catecholaminergic Polymorphic Ventricular Tachycardia. (2010)
  • Author(s): Takeshi Suetomi, Masafumi Yano, Masakazu Fukuda, Akihiro Hino, Makoto Ono, Xiaojuan Xu, Takehisa Susa, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Yasuhiro Ikeda, Masunori Matsuzaki.
  • Organizer: 83rd Scientific Session of American Heart Association.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2010-11-15
• [Presentation] Novel Inter-domain Interaction Within RyR2 as a Common Therapeutic Target by Channel Stabilization in Heart Failure and Catecholaminergic Polymorphic Ventricular Tachvcardia(CAVT) (2010)
  • Author(s): Masafumi Yano
  • Organizer: 83rd Scientific Session of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Urinary 8-Hydroxy-2'-Deoxyguanosine is a Biomarker for Evaluating the Inflammatory Activity and the Effectiveness to Corticosteroids in Patients with Cardiac Sarcoidosis (2010)
  • Author(s): Takeo Tanaka
  • Organizer: 83rd Scientific Session of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Increased Affinity of Calmodulin Binding to Cardiac Ryanodine Receptor Corrects the Defective Channel Gating in Failing Hearts (2010)
  • Author(s): Akihiro Hino
  • Organizer: 83rd Scientific Session of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Correction of Defective Calmodulin Binding to Cardiac Ryanodine Receptor Inhibits Aberrant Ca2+ Release in CPVT-associated Mutation (2010)
  • Author(s): Masakazu Fukuda
  • Organizer: 83rd Scientific Session of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Mutation-linked Defective Domain Interaction within the Ryanodine Receptor Causes Ca2+ Leak Leading to Catecholaminergic Polymorphic Ventricular Tachycardia (2010)
  • Author(s): Takeshi Suetomi
  • Organizer: 83rd Scientific Session of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-15
• [Presentation] Risk Stratification of Chronic Heart Failure by the Combination of Urinary 8-Hydroxy-2'-Deoxyguanosine and Plasma Brain Natriuretic Peptide. (2010)
  • Author(s): Takehisa Susa, Shigeki Kobayashi, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Jutaro Yamada, Takayuki Okamura, Takeshi Ueyama, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: The 14th Annual Scientific Meeting of the Japanese Heart Failure Society.
  • Place of Presentation: 東京 京王プラザホテル
  • Year and Date: 2010-10-07
• [Presentation] Mechanism of Destabilized RyR2 Channel in Catecholaminergic Polymorphic Ventricular Tachycardia. (2010)
  • Author(s): Takeshi Suetomi, Masafumi Yano, Makoto Ohno, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Masahiro Doi, Shigeki Kobayashi, Takeshi Yamamoto, Yasuhiro Ikeda, Masunori Matsuzaki.
  • Organizer: The 14th Annual Scientific Meeting of the Japanese Heart Failure Society.
  • Place of Presentation: 東京 京王プラザホテル
  • Year and Date: 2010-10-07
• [Presentation] Mechanism of Destabilized RyR2 Channel in Catecholaminergic Polymorphic Ventricular Tachycardia (2010)
  • Author(s): Takeshi Suetomi
  • Organizer: The 14th Annual Scientific Meeting of the Japanese Heart Failure Society
  • Place of Presentation: 東京
  • Year and Date: 2010-10-07
• [Presentation] Risk Stratification of Chronic Heart Failure by the Combination of Urinary 8-Hydroxy-2'-Deoxyguanosine and Plasma Brain Natriuretic Peptide (2010)
  • Author(s): Takehisa Susa
  • Organizer: The 14th Annual Scientific Meeting of the Japanese Heart Failure Society
  • Place of Presentation: 東京
  • Year and Date: 2010-10-07
• [Presentation] Correction of the defective inter-domain interaction within ryanodine receptor prevents the development of heart failure. (2010)
  • Author(s): Hitoshi Uchinoumi, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Xiaojuan Xu, Makoto Ohno, Shinichi Okuda, MasahiroDoi, Shigeki Kobayashi, Takeshi Yamamoto, Masunori Matsuzaki.
  • Organizer: 20th World Congress of the International Society for Heart Research.
  • Place of Presentation: 京都,京都国際会議場
  • Year and Date: 2010-05-13
• [Presentation] Urine 8-hydroxy-2'-deoxyguanosine is a marker for predicting mortality and morbidity as swell as evaluating the effectiveness of beta-blocker therapy in patients with chronic heart failure. (2010)
  • Author(s): Susa Takehisa
  • Organizer: ACC. 10 and i2 Summit
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2010-03-16
• [Presentation] Urine 8-hydroxy-2'-deoxyguanosine is a Marker for Predicting Mortality and Morbidity as well as Evaluating the Effectiveness of Beta-blocker Therapy in Patients with Chronic Heart Failure. (2010)
  • Author(s): Takehisa Susa, Shigeki Kobayashi, Takeo Tanaka, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Jutaro Yamada, Takeshi Ueyama, Shuji Kawamura, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: 59th Annual Scientific Session of the American College of Cardiology.
  • Place of Presentation: Atlanta, USA.
  • Year and Date: 2010-03-15
• [Presentation] Decreased Affinity of Calmodulin to the Cardiac Ryanodine Receptor Plays a Crucial Role in the CPVT-type Channel Disorder. (2010)
  • Author(s): Xiaojuan Xu, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Makoto Ohno, Hitoshi Uchinoumi, Tetsuro Oda, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Yasuhiro Ikeda, Tomoko Ohkusa, Masunori Matsuzaki.
  • Organizer: 74th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: 京都,京都国際会議場
  • Year and Date: 2010-03-05
• [Presentation] Correction of Defective Conformational Regulation of the Cardiac Ryanodine Receptor is a New Therapeutic Strategy against Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). (2010)
  • Author(s): Hitoshi Uchinoumi, Masafumi Yano, Takeshi Suetomi, Makoto Ohno, Xiaojuan Xu, Hiroki Tateishi, Tetsuro Oda, Shinichi Okuda, Masahiro Doi, Shigeki Kobayashi, Takeshi Yamamoto, Yasuhiro Ikeda, Tomoko Ohkusa, Masunori Matsuzaki.
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: 京都,京都国際会議場
  • Year and Date: 2010-03-05
• [Presentation] Interruption of Novel Inter-domain Interaction within RyR2 as a Common Therapeutic Target for Channel Stabilization in Heart Failure and CPVT. (2010)
  • Author(s): Takeshi Yamamoto, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Makoto Ohno, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Masahiro Doi, Shigeki Kobayashi, Masunori Matsuzaki.
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: 京都,京都国際会議場
  • Year and Date: 2010-03-05
• [Presentation] Urinary 8-Hydroxy-2'Deoxyguanosine as an Oxidative Stress Biomarker in Patients with Chronic Heart Failure. (2010)
  • Author(s): Shigeki Kobayashi, Takehisa Susa, Takeo Tanaka, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Yasuhiro Yoshiga, Jutaro Yamada, Takeshi Ueyama, Shuji Kawamura, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: 京都,京都国際会議場
  • Year and Date: 2010-03-05
• [Presentation] Correction of defective inter-domain interaction within the cardiac ryanodine receptor as a new therapeutic strategy against catecholaminergic polymorphic ventricular tachycardia (CPVT). (2009)
  • Author(s): Hitoshi Uchinoumi, Masafumi Yano, Takeshi Suetomi, Makoto Ohno, Xiaojuan Xu, Shigeki Kobayashi, Takeshi Yamamoto, Masunori Matsuzaki.
  • Place of Presentation: 札幌,ロイトン札幌
  • Year and Date: 2009-12-04
• [Presentation] Low-dose of β Blocker Improves Cardiac Function in Patients With Acute Heart Failure Partly by Inhibiting Ca2+ Leak Through the Ryanodine Receptor. (2009)
  • Author(s): Shigeki Kobayashi, Takeo Tanaka, Takehisa Susa, Makoto Ohno, Hitoshi Uchinoumi, Shinichi Okuda, Masahiro Doi, Shuji Kawamura, Takeshi Yamamoto, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Decreased Affinity of Calmodulin to RyR2 May Be a Sauce Mechanism of Leaky Channel in CPVT-associated Mutation. (2009)
  • Author(s): Xiaojuan Xu, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Makoto Ohno, Hitoshi Uchinoumi, Tetsuro Oda, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Yasuhiro Ikeda, Takeshi Yamamoto, Tomoko Ohkusa, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Mutation-linked Channel Disorder in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is Caused by Abnormally Tight Domain-Domain Interaction in RyR2. (2009)
  • Author(s): Takeshi Suetomi, Masafumi Yano, Akihiro Hino, Makoto Ohno, Xiaojuan Xu, Takehisa Susa, Hitoshi Uchinoumi, Tetsuro Oda, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Yasuhiro Ikeda, Takeshi Yamamoto, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Correction of Defective Inter-domain Interaction Within the Cardiac Ryanodine Receptor as a New Therapeutic Strategy Against Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). (2009)
  • Author(s): Hitoshi Uchinoumi, Masafumi Yano, Akihiro Hino, Takeshi Suetomi, Makoto Ohno, Xiaojuan Xu, Tetsuro Oda, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Yasuhiro Ikeda, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Urine 8-hydroxy-2'-deoxyguanosine is Well Correlated With Cardiac Dysfunction and Poor Prognosis in Chronic Heart Failure Patients. (2009)
  • Author(s): Takehisa Susa, Shigeki Kobayashi, Takeo Tanaka, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Yomoko Nao, Yasuhiro Yoshiga, Jutaro Yamada, Shuji Kawamura, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Urine 8-hydroxy-2'-deoxyguanosine as a New Biomarker of Inflammatory Activity in Patients With Cardiac Sarcoidosis. (2009)
  • Author(s): Takeo Tanaka, Shigeki Kobayashi, Takehisa Susa, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Tomoko Nao, Yasuhiro Yoshiga, Jutaro Yamada, Shuji Kawamura, Masafumi Yano, Masunori Matsuzaki.
  • Organizer: 82nd Scientific Session of American Heart Association.
  • Place of Presentation: Orlando, USA.
  • Year and Date: 2009-11-16
• [Presentation] Low-dose of β blocker improves cardiac function in patients with acute heart failure partly by inhibiting Ca2+leak through ryanodine receptor. (2009)
  • Author(s): Shigeki Kobayashi
  • Organizer: Scientific Sessions 2009 of American Heart Association
  • Place of Presentation: Orland, USA
  • Year and Date: 2009-11-16
• [Presentation] Low-dose βblocker therapy improves cardiac function in patients with acute heart failure partly through correction of abnormal intracellular Ca2+ handling (2009)
  • Author(s): Shigeki Kobayashi
  • Organizer: The American College of Cardiology 58^<th> Annual Scientific Session
  • Place of Presentation: Orlando, USA
  • Year and Date: 2009-03-29
• [Presentation] Dantrolene Prevents Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)by Correcting Abnormal Ca^<2+>Release through the Ryanodine Receptor (2009)
  • Author(s): Shigeki Kobayashi
  • Organizer: The 73nd Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2009-03-22
• [Presentation] Dantrolene inhibits spontaneous Ca^<2+> release as a substrate for catecholaminergic polymorphic ventricular tachycardia (CPVT)by correcting defective inter-domain interaction within the ryanodine receptor (2008)
  • Author(s): Shigeki Kobayashi
  • Organizer: Scientific Sessions 2008 of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-12
• [Remarks] ホームページ等 なし