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The basic research of multidisciplinary support for impaired left ventricle with dilated cardiomyopathy

Research Project

Project/Area Number 21390385
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKyoto University

Principal Investigator

SAKATA Ryuzo  京都大学, 大学院・医学研究科, 教授 (20325781)

Co-Investigator(Kenkyū-buntansha) IKEDA Tadashi  京都大学, 大学院・医学研究科, 准教授 (40281092)
MINAKATA Kenji  京都大学, 大学院・医学研究科, 助教 (60539675)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords拡張型心筋症 / 左室補助心臓 / 異所性心移植 / 細胞移植 / 左室形成術
Research Abstract

We first assessed the physiological and histological effect of prolonged circulatory support using heterotopic rat heart transplantion model, in which failing heart with auto-immune dilated cardiomyopathy model rat heart was transplanted to abdominal aorta of normal rat. We found that prolonged circulatory support improves contractile function and enhances the responsibility to catecholamines, on the other hand, deteriorates diastolic function and increases apoptosis of myocardium. We supposed that prolonged circulatory support might be advantageous for"bridge to transplantation", however, disadvantageous for myocardium itself. Next, we showed that the administration ofβ-blocker after experimental left ventricular volume reduction surgery demonstrates the attenuation of left ventricular remodeling. This supports the possibility to attenuate the adverse effects of prolonged circulatory support when combined with the administration of cardioprotective reagents. Considering these results, we examined that sustained topical release of cardioprotective cytokines might attenuate the myocardial damage for dilated cardiomyopathy model rat heart. Hepatocyte growth factor, which possesses potent anti-fibrotic and anti-apoptotic effect, was topically administrated for dilated cardiomyopathy model rat heart with sustained release method using gelatin hydrogel. We found that the therapy improved cardiac function and showed tendency for decreased apoptosis and fibrosis. Taken together, we indicated that the combination of prolonged circulatory support and sustained release of cardioprotective cytokines would be a promising therapeutic strategy for dilated cardiomyopathy.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (11 results)

All 2012 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Remarks (2 results)

  • [Journal Article] Pluripotent Stem Cell-Engineered Cell Sheets Re-Assembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart2012

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

      Stem Cells

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of cardioplegia with poly(ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury2012

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

      J Enzyme Inhib Med Chem

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury : in vitro study2012

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

      J Enzyme Inhib Med Chem

      Volume: (in press) Issue: 1 Pages: 143-147

    • DOI

      10.3109/14756366.2011.642373

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topical application of a biodegradable disc with amiodarone for atrial fibrillation2011

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

      Ann Thorac Surg

      Volume: 91 Issue: 3 Pages: 734-9

    • DOI

      10.1016/j.athoracsur.2010.10.022

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rrolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyo pathy accompanied by myocardial stiffness and apoptosis2010

    • Author(s)
      Muranaka H. Marui A, Tsukashita M, WangJ, Nakano J, Ikeda T, Sakata R
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery

      Pages: 1-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carvedilol may alleviate late cardiacre modelling following surgical ventricular restoration2010

    • Author(s)
      Yoshikawa E、Marui A、Tsukashita M、NisinaT、Wang J、Muranaka H、Ikeda T、Komeda M
    • Journal Title

      European Journal of Cardiothoracic Surgery

      Volume: 37(2) Pages: 362-367

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prolonged mechanical unloading preserves myocardial contractility butimpairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis2010

    • Author(s)
      Muranaka H, Marui A, Tsukashita M, Wang J, Nakano J, Ikeda T, Sakata R
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery

      Volume: Oct;140(4) Pages: 916-922

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carvedilol may alleviate late cardiac remodelling following surgical ventricular restoration2010

    • Author(s)
      Yoshikawa E, Marui A, Tsukashita M, Nishina T, Wang J, Muranaka H, Ikeda T, Komeda M.
    • Journal Title

      European Journal of Cardiothoracic Surgery

      Volume: Feb;37(2) Pages: 362-367

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prolonged mechanical unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated cardiomyopathy accompanied by myocardial stiffness and apoptosis2010

    • Author(s)
      Muranaka H., Marui A, Tsukashita M, Wang J, Nakano J, Ikeda T, Sakata R
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery (In Press)

      Pages: 1-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://www.kyoto-cvs.com/g-shinfuzen.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.kyoto-cvs.com/g-shinfuzen.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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