Do Ketone Bodies Contribute to Protection against Damage Caused by Bothmyocardial Ischemia and Reperfusion Injury?

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: seven hearts were exposed to 10 minutes of myocardial ischemia followed by 30 minutes of coronary reperfiusion with normal Krebs-Henseleit (K-H) buffer without using ketone bodies (K(-)group), and the other seven hearts were exposed to the same ischemia and reperfused with K-H buffer containing 5 mM ketone bodies(Ke group). These were compared with seven 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 AGATP 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, cytosolic ΔGATP hydrolysis energy, 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.