Promising Strategies for Metabolic Intervention in the Ischemic Heart

VELEZ, D; HERMANN, R; VARELA, A; MARINA PRENDES, MG

Horizons in World Cardiovascular Research.

Nova Science Publishers

Año: 2017; p. 1 - 19

The heart is a highly active organ that consumes 10% of the body?s total oxygen uptake and cycles 6 kg of ATP every day in order to couple energy production with energy demand. Under normal conditions, more than 95% of ATP is derived from mitochondrial oxidative phosphorylation, with the remainder being derived from anaerobic glycolysis. Heart muscle possesses a high degree of metabolic flexibility, being capable of consuming a wide variety of energy substrates. Under physiological conditions, fatty acids and glucose represent the primary metabolic fuels that support mechanical contraction, basal metabolism, and ionic homeostasis. The contribution of these substrates to energy production will change depending on the metabolic conditions. For example, during fasting, increased availability of fatty acids reduces glucose utilization in accordance with the Randle effect. During myocardial ischemia, the oxygen and substrate supply to the myocytes is not sufficient to meet the high myocardial energy demand, oxidative metabolism decreases sharply and anaerobic glycolysis, which produces an inadequate quantity of ATP and causes accumulation of potentially harmful catabolites, increases. The extent of this metabolic change depends on the severity of the ischemic episode and could determine, in part, the extent of ischemic damage. Although reperfusion is the essential prerequisite for the salvage of myocardium, it is also associated with profound disturbances that may predispose to further tissue injury, also known as reperfusion injury. During reperfusion oxidative metabolism recovers, and in the presence of high levels of fatty acids, as was found in patients suffering acute myocardial infarction, glucose oxidation is dramatically inhibited. To this respect, many studies have shown that the extent of cardiac injury is influenced by the substrate availability early during reperfusion and the substrate pattern of oxidative metabolism.In the last few years, an increasing number of clinical and experimental studies have shown that optimizing energy metabolism in the ischemic-reperfused heart, is an effective approach to decrease the detrimental effects associated with myocardial ischemia-reperfusion. This chapter focuses on how altering energy substrate metabolism in the heart can be used as an approach for the treatment of cardiac ischemia-reperfusion. It will concentrate on some of the recent advances made on these therapeutic interventions, emphasizing the importance of the metabolic manipulation in the first critical hours from symptom onset.