Metabolic cardiac protection

Several animal and clinical studies have clearly demonstrated the clinical importance of ischemia reperfusion injury (IRI) in the setting of an acute coronary syndrome (ACS). It is well known that a shift of glucose metabolism from oxidative phosphorylation to substrate level phosphorylation (glycolysis) occurs during prolonged ischemia. As a consequence, protons and lactic acid accumulate within the cells, while ATP, NADH and NAD+ dehydrogenase levels decrease. Fatty acid oxidation contribute in the ischemic myocardium to the increased production of reactive oxygen species (ROS), that participate to mitochondrial uncoupling further reducing mitochondrial efficiency and ATP production. These and other changes in cardiac metabolism contribute to the opening of the mitochondrial permeability transition pore (mPTP), responsible for myocytes apoptosis. Varieties of pharmacological approaches have been proposed to minimize IRI and maximize the myocardial salvage, than those achieved by reperfusion alone. This brief review will provide the rationale for the use of metabolic approaches to protect the heart from ischemia and during reperfusion.