| Project/Area Number |
21390385
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
SAKATA Ryuzo 京都大学, 大学院・医学研究科, 教授 (20325781)
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| 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)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| 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)
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| 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 |
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| 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.
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