| Project/Area Number |
18500358
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
UEMURA Kazunori National Cardiovascular Center Research Institute, Department of Cardiovascular Dynamics, Research Scientist (10344350)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMACHI Masaru National Cardiovascular Center Research Institute, Department of Cardiovascular dynamics, Director (40250261)
KAMIYA Atsunori National Cardiovascular Center Research Institute, Department of Cardiovascular dynamics, Research Scientist (30324370)
清水 秀二 国立循環器病センター研究所, 循環動態機能部, 派遣研究員 (80443498)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Automated control / Heart Failure / Hemodynamics / Cardiac Oxigen Metabolism / Vagal Nerve / Cardiac Matrix Metalloproteinase / Ventricular Remodeling / Acute Myocardinal Infarction / 心臓酸素消費量 / 心拡大 / 心臓間質酵素 |
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| Research Abstract |
We have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressue(AP) , cardiac output(CO) , and left atrial pressure(P_<LA>) . With this system, hemodynamics of heart failure patients after acute myocardial infarction can be automatically restored to normal condition. We further expanded our system so that the system can optimize cardiac oxygen metabolism as well as hemodynamics in such patients through precise control of heart rate reduction and ventricular inotropy. In a canine acute heart failure model, the expanded system was able to improve cardiac oxygen metabolism while restoring normal hemodynamic condition. Whether the improvement in cardiac oxygen metabolism as achieved by our system really ameliorates the myocardial damage remained to be evaluated. To answer this question, we developed an artificial arterial preparation, to which an isolated rabbit heart is connected. The preparation enables us to continuously monitor the oxygen metabolism of the rabbit heart while AP, CO, and P_<LA> are simultaneously controlled to a desired level.
Electrical stimulation of vagal nerve can be an efficient method of heart rate reduction in our system. In a rabbit model of myocardial ischemia-reperfusion injury, we investigated the effects of electrical stimulation of efferent vagal nerve on myocaidial expression and activation of Cardiac Matrix Metalloproteinase, which is known to play crucial roles in the progression of heart failure after acute myocardial infarction. We disclosed that stimulation of the efferent vagal nerve increased mRNA and protein level of endogenous inhibitor of Cardiac Matrix Metalloproteinase(TIMP-1) , and reduced activity of Cardiac Matrix Metalloproteinase. This means that vagal stimulation can be not only an effective method of heart rate reduction, but also an effective method of cardio protection in acute heart failure.
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