| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
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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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