The heart is known for its ability to produce energy from
fatty acids (FA) because of its important beta-oxidation equipment, but it can also derive energy from several other substrates including
glucose,
pyruvate, and
lactate. The cardiac
ATP store is limited and can assure only a few seconds of beating. For this reason the cardiac muscle can adapt quickly to the energy demand and may shift from a 100% FA-derived energy production (after a
lipid-rich food intake) or any balanced situation (e.g., diabetes, fasting, exercise). These situations are not similar for the heart in terms of
oxygen requirement because
ATP production from
glucose is less
oxygen-consuming than from FA. The regulation pathways for these shifts, which occur in physiologic as well as pathologic conditions (
ischemia-reperfusion), are not yet known, although both
insulin and
pyruvate dehydrogenase activation are clearly involved. It becomes of strategic importance to clarify the pathways that control these shifts to influence the
oxygen requirement of the heart. Excess FA oxidation is closely related to myocardial contraction disorders characterized by increased oxygen consumption for cardiac work. Such an increased
oxygen cost of cardiac contraction was observed in
stunned myocardium when the contribution of FA oxidation to oxygen consumption was increased. In rats, an increase in n-3 polyunsaturated FA in heart
phospholipids achieved by a
fish-oil diet improved the recovery of pump activity during postischemic reperfusion. This was associated with a moderation of the
ischemia-induced decrease in mitochondrial
palmitoylcarnitine oxidation. In isolated mitochondria at
calcium concentrations close to that reported in ischemic cardiomyocytes, a futile cycle of
oxygen wastage was reported, associated with energy wasting (constant
AMP production). This occurs with
palmitoylcarnitine as substrate but not with
pyruvate or
citrate. The energy wasting can be abolished by
CoA-SH and other compounds, but not the
oxygen wasting. Again, the
calcium-induced decrease in mitochondrial
ADP/O ratio was reduced by increasing the n-3 polyunsaturated FA in the mitochondrial
phospholipids. These data suggest that in addition to the amount of circulating
lipids, the quality of FA intake may contribute to heart energy regulation through the
phospholipid composition. On the other hand, other intervention strategies can be considered. Several studies have focused on
palmitoylcarnitine transferase I to achieve a reduction in beta-oxidation. In a different context,
trimetazidine was suggested to exert its anti-ischemic effect on the heart by interfering with the metabolic shift, either at the
pyruvate dehydrogenase level or by reducing the beta-oxidation. Further studies will be required to elucidate the complex system of heart energy regulation and the mechanism of action of potentially efficient molecules.