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

研究了酮体对实验性心肌缺血心肌功能和线粒体能量的影响，重点研究了再灌注损伤后的心肌功能。21只离体大鼠心脏缺血后按灌注方式分为三类：7只心脏缺血10 min后冠脉再灌注正常Krebs-Henseleit （K- h）缓冲液30 min，不使用酮体（K（-）组），其余7只心脏同样缺血后再灌注含有5 mM酮体的K- h缓冲液（Ke组）。将其与7颗正常心脏（对照组）进行比较。心脏表现通过几个指标来评估：最大dp/dt、心输出量、心功和心脏效率。利用线粒体氧化还原态、电位和胞质△GATP水解能估算线粒体能量。结果表明，再灌注后，Ke组左室收缩力的改善比K（-）组更快。从能量学的角度来看，酮体似乎经济地增加了线粒体代谢，因为线粒体氧化还原状态（Eh NAD/NADH: C=280.8 mV, Ke=297.1 mV， K(-)=291.1 mV），胞质△GATP水解能（△GATP: C=56.4 KJ/mol, Ke=58.2 KJ/mol， K(-)=56.0 KJ/mol）和磷酸肌酸浓度显著增加。由此可见，在心肌缺血时，酮体作为底物产生线粒体能量，并通过这一功能保护心肌免受短暂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.