| Project/Area Number |
16390225
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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 |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
HORIO Masatsugu Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20124779)
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| Co-Investigator(Kenkyū-buntansha) |
KITAKAZE Masafumi National Cardiovascular Center, Department of Cardiovascular Clinical Research, Director, 臨床開発部, 部長 (20294069)
TOYOFUKU Toshihiko Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60322179)
TAKEDA Hiroshi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20127252)
MINAMINO Tetsuo Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30379234)
TAKASHIMA Seiji Osaka University, Health Care Center, Assistant, 保健センター, 助手 (90379272)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2004: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | myocardial infarction / heart failure / preconditioning / adenosine / nitric oxide |
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| Research Abstract |
In the developed country, arrhythmia and subsequent heart failure after myocardial infarction have been major cause of cardiac death. This study was designed to elucidate the mechanism of cardiovascular injury after acute myocardial infarction and develop the novel method to protect myocardial damage after ischemic stress. We especially examined the ischemia preconditioning phenomenon and role of vasodilatation after brief ischemia using rat or canine ischemia model.
In this study, we showed that production of NO and K channel opener mimicked ischemic preconditioning. Adenosine was also revealed to have cardioprotective effect after ischemia suggesting adenosine and NO pathway plays an important role of ischemia preconditioning phenomenon. Then we showed that common anti-hypertensive medicine carvedirol and amlodipine protect ischemic injury by vascular dilation via production of NO and adenosine. Intracellular signaling of adenosine and NO was also examined and revealed the involvement of PKC and PKA in this protective effect.
Since we concluded that NO and adenosine are key molecules for protecting these ischemic damages, we started the clinical use of adenosine signal enhancer for heart failure. We will continue to examine the effect of adenosine for cardiovascular function in various conditions clinically and experimentally.
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