| Project/Area Number |
16591421
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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 | Kinki University |
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Principal Investigator |
NISHIWAKI Noboru Kinki University, Hospital, Professor, 医学部附属病院, 教授 (70319739)
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| Co-Investigator(Kenkyū-buntansha) |
KANEDA Kouzou Kinki University, Hospital, Lecturer, 医学部附属病院, 講師 (40340830)
KOMEDA Masashi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (20303810)
SAJI Yoshiaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00399776)
大野 暢久 京都大学, 医学研究科, 助手 (40303838)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Cardioplegia / PARP inhibitor / Ischemia-reperfusion injury / Oxidative stress / 8-OHdG / 心筋虚血再灌流障害 |
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| Research Abstract |
Ischemic-reperfusion injury has been one of the most serious problem even in current cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury by preventing energy depletion associated with oxidative stress. The purpose of our study was to evaluate the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest.
Isolated rat hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution (St.Thomas solution) given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n=8) were perfused with a standard cardioplegic solution and terminal warm cardioplegia, whereas the 3-AB(+) group (n=8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis.
During reperfusion, the 3-AB(+) group showed significantly higher (P=0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK ; P=0.003 GOT ; P<0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P<0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P=0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group.
In conclusion, cardioplegic solution supplemented with PARS inhibitor provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress.
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