| Project/Area Number |
07671467
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAWA Yoshiki Osaka University Medical School, Assistant Professor, 医学部, 助手 (00243220)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toshiki Osaka University Medical School, Assistant Professor, 医学部, 助手 (50263257)
MASAI Takafumi Osaka University Medical School, Assistant Professor, 医学部, 助手 (30273650)
KADOBA Keishi Osaka University Medical School, Lecturer, 医学部, 講師 (00185886)
SHIRAKURA Ryota Osaka University Medical School, Professor, 医学部, 教授 (00116047)
谷口 和博 大阪大学, 医学部, 助手 (90171842)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Myocardial Protection / Ischemia-Reperfusion Injury / Non-Depolarizing Cardioplegia / AP4A / Nicorandil / HVJ-liposome / HSP 70 / HSP70 / 虚血再潅流 |
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| Research Abstract |
Calcium overload induced by ischemia-reperfusion injury of the heart is regarded as a main cause of the reduction of contractility, abnormal automacitity and myocardial cell death. Hyper-kalemic depolarizing cardioplegia which is widely used has a disadvantage in the aspect of Ca overload. In this study, we performed in vitro, in vivo and clinical examination for creating a non-depolarizing cardioplegia. invitro study We established the method to measure membrane current of isolated rat cardiomyocytes, using the patch clamp method. We measured Na/K pump current of isolated rat cardiomyocyte and certificated the Na/K pump imhibition effects of Nafamostat mesilate. in vivo study AP4A is a P2y receptor agonist, and has an ability of openingv effect of ATP sensitive potassium channel (1_<KATP>). The myocardial protective effects of AP4A were evaluated using Langendorff perfusion of isolated rat heart. Preischemic infusion of AP4A significantly improved the post ischemic functional recovery. The myocardial protective effects of AP4A was similar to ischemic preconditioning. These results suggested that AP4A is a possible component of non-depolarizing cardioplegia. The transfection of Na/Ca exchanger expression gene can reinfore the myocardial tolerance against ischemia-reperfusion injury. We established the effective gene transfection method using HVJ-liposome method. Using this method, the protective effects of induced HSP 70 protein were examined. clinical study Nicorandil which is one of the clinical used coronary arterial dilator has IKATP opening properties. The addition of Nicorandil to cardioplegia may reduce Ca overload induced by depolarizing cardioplegia. The clinical evaluations of the efficacy of Nicorandil added to cardiopulmonary bypass in cases of coronary artery bypass grafting are now on going.
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