The study of mechanisms and prevention of arrhythmogenetic remodeling of ventricular myocardium caused by oxidative stress under hyperglycemic state.

• Project/Area Number: 25461071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tamagawa University
• Principal Investigator: HIROE Niwano 玉川大学, 教育学部, 教授 (00293233)
• Co-Investigator(Kenkyū-buntansha): NIWANO Shinichi 北里大学, 医学部, 准教授 (70282978)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 酸化ストレス / SOD欠損マウス / 不整脈基盤 / 糖尿病 / 1型糖尿病 / 電気的リモデリング / 不整脈基盤形成 / Sod2+/-マウス / Sod2-/-線維芽細胞 / EUK-8 / H/M-Sod2欠損マウス / 不整脈

Outline of Final Research Achievements

In this study, hyperglycemic state was induced by the injection of streptozotocin (STZ) in heart/muscle-specific manganese superoxide dismutase-hetero deficient (H/M-Sod2+/-) mice and the myocardial electoro-physiological status was evaluated. In this model mice, we documented the hyper-production of reactive oxygen species(ROS) and the electrical remodeling which characterized by prolongation in ERP and MAPD with the increase of inducibility of ventricular arrhythmia. Also, EUK-8 (the SOD/catalase mimetic) treatment diminished the ROS production independently to the hyperglycemic condition, and suppressed these electoro-physiological changes. This result may indicate the importance of oxidative stress in promotion of the electrical remodeling in acute hyperglycemic state.

Research Products

• [Journal Article] Efficacy and Limitations of Tachycardia Detection Interval Guided Reprogramming for Reduction of Inappropriate Shock in Implantable Cardioverter-Defibrillator Patients (2016)
  • Author(s): Tamami Fujiishi, Shinichi Niwano, Masami Murakami, Hironori Nakamura, Tazuru Igarashi, Naruya Ishizue, Jun Oikawa, Jun Kishihara, Hidehira Fukaya, Hiroe Niwano, and Junya Ako
  • Journal Title: International Heart Journal Volume: 57 No.3 Pages: 201-211
  • NAID: 130005153703
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-derived Mitochondrial Superoxide Causes Myocardial Electrical Remodeling by Down-regulating Potassium Channels and Related Molecules (2014)
  • Author(s): Kurokawa S, Niwano S, Niwano H, Ishikawa S, Murakami M, Kosukegawa T, Masaki Y, Tamaki H, Toda T, Noda Y, Shimizu T, Izumi T.
  • Journal Title: Circulation Journal Volume: 78 Pages: 1950-1959
  • NAID: 130004427935
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation. (2014)
  • Author(s): Kisihara J, Niwano S, Niwano H, Aoyama Y, Satoh A, Oikawa J, Kiryu M, Fukaya H, Masaki Y, Tamaki H, Izumi T, Ako J
  • Journal Title: Cardiovascular Diagnosis and Therapy Volume: 4
  • Peer Reviewed / Open Access
• [Journal Article] Role of Endothelial Dysfunction in Thrombus Formation in the Left Atrium. Protective Role of Nitric Oxide Synthesis in the Syrface of Atrium. (2014)
  • Author(s): Niwano S
  • Journal Title: Circulation Journal Volume: 78 Pages: 1841-1842
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of new onset atrial fibrillation through P wave analysis in 12 lead ECG. (2014)
  • Author(s): Yoshizawa T, Niwano S, Niwano H, Igarashi T, Fujiishi T, Ishizue N, Oikawa J, Satoh A, Kurokawa S, Hatakeyama Y, Fukaya H, Ako J
  • Journal Title: International Heart Journal Volume: 55 Pages: 422-427
  • NAID: 130004678102
  • Peer Reviewed / Open Access
• [Journal Article] Sudden cardiac arrest recorded during Holter monitoring: prevalence, antecedent electrical events, and outcomes. (2014)
  • Author(s): Watanabe E, Tanabe T, Osaka M, Chishaki A, Takase B, Niwano S, Watanabe I, Sugi K, Katoh T, Takayanagi K, Mawatari K, Horie M, Okumura K, Inoue H, Atarashi H, Yamaguchi I, Nagasawa S, Moroe K, Kodama I, Sugimoto T, Aizawa Y
  • Journal Title: Heart Rhythm Volume: 8 Pages: 1418-1425
  • Peer Reviewed / Open Access
• [Journal Article] Prophylactic attain administration may prevent shortening of the fibrillation cycle length in patients with new onset atrial fibrillation. (2013)
  • Author(s): Oikawa J, Niwano S, Niwano H, Ishizue N, Yoshizawa T, Satoh A, Kurokawa S, Hatakeyama Y, Fukaya H.
  • Journal Title: International Heart Journal Volume: 2013; 54: 371-6. Pages: 371-376
  • Peer Reviewed
• [Presentation] Prediction of Upcoming Therapeutic Episodes of ICD through Routine Data in Periodic Device Clinic of ICD Patients. (2015)
  • Author(s): Fujiishi T, Niwano S, Murakami M, Nakamura H, Igarashi T, Ishizue N, Oikawa J, Kishihara J, Fukaya H, Niwano H, Ako J.
  • Organizer: American heart Association Scientific Sessions 2015
  • Place of Presentation: Ｏｒｌａｎｄ（ＵＳＡ）
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Aliskiren Suppresses Extracellular Matrix Genes in Atrial Fibrillation - A Global mRNA Profiling in the Canine Experimental Atrial Fibrillation Model. (2015)
  • Author(s): Kishihara J, Niwano S, Niwano H, Satoh A, Igarashi T, Ishizue N, Fujiishi T, Yoshizawa T, Murakami M, Fukaya H, Ako J.
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: Ｌｏｎｄｏｎ（ＵＫ）
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Linagliptin, a DPP-4 Inhibitor, Suppresses the Electrical Remodeling and Myocardial Injury in Isoproterenol-induced Myocardial Injury Model in Rat. (2015)
  • Author(s): Ishizue N, Niwano S, Nakamura H, Igarashi T, Fujiishi T, Yoshizawa T, Oikawa J, Kishihara J, Murakami M, Fukaya H, Niwano H, Ako J.
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: Ｌｏｎｄｏｎ（ＵＫ）
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Structural Remodeling in Atrium can be Suppressed by Febuxostat, a Xanthine Oxidase -Inhibitor, in the Canine Model of Atrial Fibrillation. (2015)
  • Author(s): Yoshizawa T, Niwano S, Niwano H, Igarashi T, Nakamura H, Fujiishi T, Ishizue N, Kishihara J, Murakami M, Fukaya H, Ako J.
  • Organizer: Heart Ryththm 2015
  • Place of Presentation: Ｂｏｓｔｏｎ（ＵＳＡ）
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] Effect of TDI Guided Reprogramming to Reduce Inappropriate Shock in ICD Patients and Clinical Predicting Factor Even After the Repeated-Reprogramming. (2015)
  • Author(s): Fujiishi T, Niwano S, Murakami M, Nakamura H, Igarashi T, Ishizue N, Yoshizawa T, Kishihara J, Fukaya H, Niwano H, Ako J.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Discrimination of Paroxysmal and Non-paroxysmal Atrial Fibrillation In the Patients with New-onset Atrial Fibrillation. (2015)
  • Author(s): Igarashi T, Niwano S, Ishizue N, Fujiishi T, Yoshizawa T, Kishihara J, Fukaya H, Niwano H, Ako J.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2015-04-24
  • Int'l Joint Research
• [Presentation] Antiepileptic medicines increase the prevalence of Brugada-type ST elevation in patients with epilepsy. (2014)
  • Author(s): Ishizue N, Niwano S, Saitou M, Igarashi T, Fujiishi T, Yoshizawa T, Kishihara J, Murakami M, Fukaya H, Niwano H, Miyaoka H, Ako J
  • Organizer: American Heart Assiciation, Congress 2014
  • Place of Presentation: chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Arrhythmias and Myocaridal Remodeling in Autoimmune Myocarditis Model. Symposium in Annual Meeting of The Japanese Heart Rhythm Society. (2014)
  • Author(s): Niwano S.
  • Organizer: the 29th Annual Meeting of the Japanese Heart Rhythm Society
  • Place of Presentation: The Prince Park Tower Tokyo, Tokyo, Japan
  • Year and Date: 2014-07-22 – 2014-07-25
  • Invited
• [Presentation] Prevalence of Brugada-type ST Elevation and J-wave Like QRS Abnormality in Patients Receiving Antiepileptic Drugs. (2014)
  • Author(s): Ishizue N, Niwano S, Yoshizawa T, Oikawa J, Fukaya H, Satoh A, Niwano H.
  • Organizer: the 29th Annual Meeting of the Japanese Heart Rhythm Society
  • Place of Presentation: The Prince Park Tower Tokyo,Tokyo, Japan
  • Year and Date: 2014-07-22 – 2014-07-25
• [Presentation] P Wave Morphological Changes in Surface ECG in Cases with New Onset Atrial Fibrillation. (2014)
  • Author(s): Yoshizawa T, Niwano S, Ishizue N, Oikawa J, Satoh A, Fukaya H, Niwano H, Ako J
  • Organizer: the 29th Annual Meeting of the Japanese Heart Rhythm Society
  • Place of Presentation: The Prince Park Tower Tokyo, Tokyo, Japan
  • Year and Date: 2014-07-22 – 2014-07-25
• [Presentation] Use of statins suppress the shorting of the fibrillation cycle length in patients with new-onset atrial fibrillation -Possible anti-remodeling effect of statin for atrial structural remodeling. (2013)
  • Author(s): Oikawa J, Niwano S, Ishizue N, Yoshizawa T, Satoh A, Kurokawa S, Hatakeyama Y, Fukaya H, Niwano H.
  • Organizer: European Society of Cardiology, Congress 2013
  • Place of Presentation: Amsterdam, Nederland
• [Presentation] “PAF predicting score” for distinction of paroxysmal and non-parox ysmal atrial fibrillation by using clinical parameters and fibrillation cycle length in the surface ECG. (2013)
  • Author(s): Oikawa J, Niwano S, Niwano H, Ishizue N, Yoshizawa T, Satoh A, Kurokawa S, Hatakeyama Y, Fukaya H, Ako J.
  • Organizer: American Heart Association, Congress 2013
  • Place of Presentation: Dallas, USA
• [Presentation] Febuxostat Prevents Atrial Remodeling via Decreasing Production of Reactive Oxygen Species in Canine Model of Atrial Fibrillation. (2013)
  • Author(s): Yoshizawa T, Niwano S, Niwano H, Ishizue N, Oikawa J, Satoh A, Kurokawa S, Hatakeyama Y, Fukaya H, Ako J.
  • Organizer: American Heart Association, Congress 2013
  • Place of Presentation: Dallas, USA