1999 Fiscal Year Final Research Report Summary
Doketone Bodies Contribute to Protect Agaist Damage Caused by Both Myocardial Ischemia and Reperfusion Injury?
| Project/Area Number |
09670747
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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 |
Circulatory organs internal medicine
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| Research Institution | Kitasato University |
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Principal Investigator |
SATO Kiyotaka Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (40225933)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Takashi Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (30165716)
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| Project Period (FY) |
1997 – 1999
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| Keywords | reperfusion unjury / ischemic heart / ketone body / mitochondria / respiratory chain |
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| Research Abstract |
Effects of ketone bodies on cardiac performance and mitochondrial energetics were investigated in experimental myocardial ischemia with a special focus on the following reperfusion injury.
Twenty-one isolated rat hearts were classified into three categories by perfusion mode after ischemia: 7 hearts were exposed to 10 min of myocardial ischemi a and followed by 30 min of coronary reperfusion with normal Krebs-Henseleit (K-H) buffer without using ketone bodies (K(-) group), and the other 7 hearts were exposed to the same ischemia and reperfused with K-H buffer containing 5 mM ketone bodies-(Ke group). These were compared with 7 normal hearts, that were exposed to neither ischemia nor reperfusion (control group). Cardiac performance was assessed by several indices: max dp/dt, cardiac output, cardiac work, and cardiac efficiency. Mitochondrial energetics were estimated by using mitochondrial redox state, its potentiality and cytosolic △GATP hydrolysis energy.
As a result, the Ke group demonstrated a more rapid improvement of LV contractility than the K(-) group after reperfusion. From the standpoint of energetics, the ketone bodies seemed to economically augment the mitochondrial metabolism, because the mitochondrial redox state(Eh NAD/NADH: C=280.8 mV, Ke=297.1 mV, K(-)=291.1 mV), cytosolic △GATP hydrolysis energy (△GATP: C=56.4 KJ/mol, Ke=58.2 KJ/mol, K(-)=56.0 KJ/mol) and concentration of phosphocreatine were remarkably increased.
Thus, it was concluded that, in myocardial ischemia, ketone bodies function as a substrate to produce mitochondrial energy, and through this function, work to protect the myocardium against both transient ischemia and the following reperfusion injury.
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