This review article discusses pharmacological approaches to optimizing myocardial metabolism during
ischemia.
Fatty acids are the main fuel for the healthy heart, with a lesser contribution coming from the oxidation of
glucose and
lactate. Myocardial ischaemia dramatically alters fuel metabolism, causing an accelerated rate of
glucose conversion to
lactate and a switch from
lactate uptake by the heart to
lactate production. This causes a dramatic disruption in cell homeostasis (e.g.
lactate accumulation and a decrease in pH and
ATP). Paradoxically, moderately ischemic tissue (approximately 50% of normal flow) continues to derive most of its energy (50-70%) from the oxidation of
fatty acids despite a high rate of
lactate production. This ischaemia-induced disruption in cardiac metabolism can be minimized by metabolic agents that reduce
fatty acid oxidation and increase the combustion of
glucose and
lactate, resulting in clinical benefit to the ischemic patient. Agents that inhibit
fatty acid beta-oxidation, such as
ranolazine and
trimetazidine, have proven to be effective in the treatment of
stable angina. Treatment of acute
myocardial infarction patients with an infusion of the
glucose-
insulin-
potassium, which results in suppression of myocardial
fatty acid oxidation and greater
glucose combustion, has proven effective in reducing mortality. These metabolic
therapies are free of direct hemodynamic or chronotropic effects, and thus are well positioned for use alongside traditional agents such as
beta-adrenergic receptor antagonists or
calcium channel antagonists.