Cardiac energetics during ischaemia and the rationale for metabolic interventions.

Cardiac work is supported by high rates of combustion of carbon fuel and oxygen consumption. Fatty acids are the main fuel for the healthy heart, supplying approximately 60-80% of the energy. The balance of the energy comes from the oxidation of glucose and lactate. ATP is broken down to fuel contractile work. ATP is resynthesized in the mitochondria using energy from the oxidation of fatty acids, glucose, and lactate. Myocardial ischaemia dramatically alters fuel metabolism. Ischaemia occurs when the coronary blood flow is insufficient to supply enough oxygen to combust carbon fuels and resynthesize ATP at the normal rate. During partial reductions in coronary blood flow (30-60% of normal) there is a proportional decrease in the rates of oxygen consumption and production of ATP, and an increase in uptake of glucose by the heart. However, unlike under normal aerobic conditions, the glucose taken up by the ischaemic myocardium is not readily oxidized in the mitochondria, but rather is converted to lactate and there is a switch from uptake of lactate by the heart to lactate production. This causes a dramatic disruption in cell homeostasis: ATP content decreases; there is accumulation of lactate and H+, a fall in intracellular pH and a decrease in contractile work. Paradoxically, the ischaemic tissue continues to derive most of its energy (50-70%) from the oxidation of fatty acids despite there being a high rate of lactate production. This ischaemia-induced disruption of cardiac metabolism can be minimized by metabolic agents that decrease oxidation of fatty acids and increase the rates of combustion of glucose and lactate, resulting in clinical benefit to the ischaemic patient.