Doketone Bodies Contribute to Protect Agaist Damage Caused by Both Myocardial Ischemia and Reperfusion Injury?

为探讨酮体对实验性心肌缺血后心功能和线粒体能量的影响，将21只大鼠离体心按缺血后再灌流方式分为3组：7只大鼠心肌缺血10min，再用常规K-H缓冲液冠脉再灌注30min(K(-)组)，其余7只心脏缺血后再灌流含5 mM酮体的K-H缓冲液。并与7例既无缺血也无再灌流的正常心脏(对照组)进行比较。心功能通过以下几个指标进行评估：最大dp/dt、心输出量、心做功和心效率。用线粒体氧化还原状态、氧化还原电位和胞浆GATP水解能来评价线粒体能量学，结果表明，再灌流后，KE组较K(-)组心肌收缩能力改善更快。从能量学的角度来看，酮体似乎经济地增强了线粒体的代谢，因为线粒体的氧化还原状态(EhNAD/NADH：C=280.8 mV，Ke=297.1 mV，K(-)=291.1 mV)，胞浆GATP水解能(GATP：C=56.4kJ/m ol，Ke=58.2kJ/m o l，K(-)=56.0kJ/m o l)和磷酸肌酸浓度显著增加。因此，在心肌缺血时，酮体作为底物产生线粒体能量，并通过这种作用保护心肌免受短暂性缺血和随后的再灌注损伤。

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.