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The combined use of HGF gene therapy and ventricular assist device improves left ventricular function and enables bridge to recovery in goat model of severe heart failure

Research Project

Project/Area Number 14370411
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

MATSUMIYA Goro (2003)  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20314312)

高橋 俊樹 (2002)  大阪大学, 医学系研究科, 講師 (50263257)

Co-Investigator(Kenkyū-buntansha) MATSUDA Hikaru  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00028614)
SAWA Yoshiki  Osaka University, Hospital, Associate Professor, 医学部附属病院, 助教授 (00243220)
FUKUSHIMA Norihide  Osaka Univ, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30263247)
TAKANO Hiroshi  Osaka Univ, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70346196)
ICHIKAWA Hajime  Osaka Univ, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (60303939)
宮本 裕治  大阪大学, 医学系研究科, 講師 (80229898)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordssevere heart failure / ventricular assist device / bridge to recovery / regeneration therapy / Hepatocyte Growth Factor / LV remodeling / gene therapy / 心筋再生因子 / 左室リモデリング / Bridge to Recovery
Research Abstract

Patients with end-stage heart failure require several months and even years under ventricular assist device (VAD) until receiving heart transplantation. Therefore, additional therapy such as regeneration therapy that promotes recovery of cardiac function is desired.
In this study, we performed gene therapy with Hepatocyte Growth Factor (HGF) in the goat heat failure model requiring VAD support and examined the possibility of "bridge to recovery".
Six adult goats (56-65kg) underwent ligation of the left anterior descending coronary artery, developed severe congestive heart failure and received the implantation of biventricular VAD (BiVAD). The HGF group was administered HGF c-DNA-plasmid of 2.0mg directly in myocardium, and the control group was administered empty plasmid.
Under the BiVAD support, all goats maintained good systemic circulation and LV unloading for four weeks and after that periods we tried weaning from VAD. The HGF group showed good hemodynamics after the removal of VAD, while the control group showed the significant deterioration of hemodynamic condition. The %FS was significantly improved and LV dilatation was markedly suppressed in the HGF group than the control group (HGF vs. control, %FS;36±0.8vs24±0.6%, LVDd;34±2vs46±2mm, p<0.05). Histologically, vascular density around the infarcted area was markedly increased, and fibrous change was suppressed in the HGF group.
In conclusion, these results suggest that gene therapy using HGF may increase the chance of "bridge to recovery" in the impaired heart requiring VAD support.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All 2003 2002 Other

All Journal Article (7 results) Publications (3 results)

  • [Journal Article] Successful treatment of Novacor pump pocket infection by omental transposition.2003

    • Author(s)
      Matsumiya Goro
    • Journal Title

      Ann Thorac Surg 75・1

      Pages: 287-288

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor.2003

    • Author(s)
      Funatsu Toshihiro
    • Journal Title

      J Thorac Cardiovasc Surg 124・6

      Pages: 1099-1105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Gene transfection of hepatocyte growth factor attenuates cardiac remodeling in the canine heart : A novel gene therapy for cardiomyopathy.2002

    • Author(s)
      Ahmet Ismyle
    • Journal Title

      J Thorac Cardiovasc Surg 124・5

      Pages: 957-963

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Therpetitic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor.2002

    • Author(s)
      Funatsu Toshihiro
    • Journal Title

      J Thorac Cardiovase Surg 124・6

      Pages: 1099-1105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Gene transfection of hepatocyte growth factor ateenuates cardiac remodeling in the canine heart : A novel gene therapy for cardiomyopathy.2002

    • Author(s)
      Ahmet Ismyle
    • Journal Title

      J Thorac Cardiovasc Surg 124・5

      Pages: 957-963

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Gene transfection with human Hepatocyte Growth Factor cDNA plasmid attenuates cardiac remodeling following acute myocardial infarction in goat hearts implanted with ventricular assist devices.

    • Author(s)
      SHirakawa Yukitoshi
    • Journal Title

      J Thorac Candiovasc Surg In press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Gene transfection with human hepatocyte Growth Factor cDNA plasmid attenuates cardiac remodeling following acute myocardial infarction in goat hearts implanted with ventricular assist devices.

    • Author(s)
      Shirakawa Yukitoshi
    • Journal Title

      J Thorac Cardiovase Surg (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumiya Goro: "Successful treatment of Novacor pump pocket infection by omental transposition"Ann Thorac Surg. 75・1. 287-288 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Funatsu Toshihiro: "Therapeutic angiogenesis in the ischemic canine heart induced by myocardial injection of naked complementary DNA plasmid encoding hepatocyte growth factor"J Thorac Cardiovasc Surg. 124・6. 1099-1105 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ahmet Ismyle: "Gene transfection of hepatocyte growth factor attenuates cardiac remodeling in the canine heart : A novel gene therapy for cardiomyopathy"J Thorac Cardiovasc Surg. 124・5. 957-963 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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