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Key factors for cardiac recovery in patients with left ventricular assist device for end stage heart failure

Research Project

Project/Area Number 20591645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionNational Cardiovascular Center Research Institute (2009-2010)
Osaka University (2008)

Principal Investigator

FUJITA Tomoyuki  独立行政法人国立循環器病研究センター, 心臓血管外科, 医師 (10457012)

Co-Investigator(Kenkyū-buntansha) SAWA Yoshiki  大阪大学, 医学系研究科, 教授 (00243220)
ICHIKAWA Hajime  独立行政法人国立循環器病研究センター, 小児心臓外科, 医長 (60303939)
MATSUMIYA Goro  千葉大学, 大学院・医学研究院, 教授 (20314312)
KURATANI Toru  大阪大学, 医学系研究科, 准教授 (90448035)
UENO Takayoshi  大阪大学, 医学系研究科, 講師 (60437316)
SAKAGUCHI Taichi  大阪大学, 医学系研究科, 寄附講座准教授 (10467574)
SHIRAKAWA Yukitoshi  大阪大学, 医学系研究科, 助教 (20457013)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords心不全 / LVAD / 細胞治療 / 線維化 / リモデリング / LVAS / remodeling / ベッカー型筋ジストロフィー / 僧帽弁逆流 / 心機能 / 重症心不全 / 左室補助装置(LVAS) / recovery(回復) / reverse remodeling / 心電図同期MDCT / カラーカイネーシス / 左室unloading(負荷の軽減)
Research Abstract

Left ventricular assist device(LVAD) confers mechanical unloading to the patients in end stage heart failure to recover their own cardiac function. The mechanical unloading leads reverse remodeling which decreases LV diastolic and systolic diameter and increases LV ejection fraction. However, we found there are responders and non-responders. Among 34 patients who underwent LVAD-off test, 9 patients successfully recovered their own cardiac function and was weaned off from LVAD. The pathological examination revealed that less fibrosis and smaller cell size in these 9 patients. Therefore, we concluded that Cardiac fibrosis and myocyte size at the time of LVAD implantation were significant predictors of degree of improvement of cardiac function and the sustained recovery after the LVAD explantation.
Next, we examined cell transplantation to the patients who were unlikely recovered their own cardiac function because of their etiology of heart failure.
Simultaneous injection of autologous bone … More marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device(LVAD) implantation.
Four patients(age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium.
No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7×10(7) to 3.0×10(8), and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by H(2)(15) O positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients.
As a conclusion, the key is a viable myocytes to respond any kind of treatment such as mechanical unloading and cell transplantation. In addition, cell stability is another important factor for successful cell therapy. Less

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (10 results)

All 2011 2010 2009 2008

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (2 results) Book (2 results)

  • [Journal Article] Clinical impact of combined transplantation of autologous skeletal myoblasts and bone marrow mononuclear cells in patients with severely deteriorated ischemic cardiomyopathy2011

    • Author(s)
      Fujita T, Sakaguchi T, Miyagawa S, Saito A, Sekiya N, Izutani H, Sawa Y
    • Journal Title

      Surg Today

      Volume: 41(8) Pages: 1029-36

    • NAID

      10029284004

    • Related Report
      2010 Final Research Report
  • [Journal Article] Clinical Impact of Combined Transplantation of Autologous Skeletal Myoblasts and Bone Marrow Mononuclear Cells in Patients with Severely Deteriorated Ischemic Cardiomyopathy2011

    • Author(s)
      Fujita Tomoyuki
    • Journal Title

      Surgery Today

      Volume: (In Press)

    • NAID

      10029284004

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac fibrosis and cellular hypertrophy decrease the degree of reverse remodeling and improvement in cardiac function during left ventricular assist2010

    • Author(s)
      Saito S, Matsumiya G, Sakaguchi T, Miyagawa S, Yamauchi T, Kuratani T, Sawa Y
    • Journal Title

      J Heart Lung Transplant

      Volume: 29(6) Pages: 672-9

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cardiac fibrosis and cellular hypertrophy decrease the degree of reverse remodeling and improvement in cardiac function during left ventricular assist.2010

    • Author(s)
      Saito Shunsuke
    • Journal Title

      J Heart Lung Transplant

      Volume: 6 Pages: 672-679

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fifteen-year experience with Toyobo paracorporeal left ventricular assist system.2009

    • Author(s)
      Saito S
    • Journal Title

      J Artif Organs. 12

      Pages: 27-34

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noninvasive assessment of cardiac function during ventricular assist system support using 64-row multi-detector computed tomographic angiography2008

    • Author(s)
      Takeda K. Matsumiya G, Matsue H, Hamada S, Sakaguchi T, Fujita T, Sawa Y
    • Journal Title

      Journal of Thoracic Cardiovascular Surgery 136 (6)

      Pages: 16021603-16021603

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] LVAS装着患者における脳出血の発生原因とその対策2010

    • Author(s)
      藤田知之
    • Organizer
      第48回人工臓器学会
    • Place of Presentation
      仙台
    • Year and Date
      2010-11-09
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] LVAS装着患者に対する抗凝固療法と頭蓋内出血に対する第IX因子複合体製剤の有用性について2009

    • Author(s)
      藤田知之
    • Organizer
      第47回人工臓器学会
    • Place of Presentation
      新潟
    • Year and Date
      2009-11-13
    • Related Report
      2009 Annual Research Report
  • [Book] 心不全急性期の非薬物療法に親しむ、弁修復・弁置換2010

    • Author(s)
      藤田知之、小林順二郎
    • Publisher
      中山書店
    • Related Report
      2010 Final Research Report
  • [Book] 循環器臨床サピア8 心不全の急性期対応2010

    • Author(s)
      藤田知之, 他
    • Total Pages
      282
    • Publisher
      中山書店
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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