Cardiac metabolism in ischemic heart disease.

Myocardial ischemia is the metabolic consequence of an inadequate blood supply to the myocardium. How does the myocardium survive a severe insult? Ischemia, perhaps acting through hypoxia, is able to induce a series of cellular signals that lead to protective genetic reprogramming. Metabolic self-protection includes the new ischemic syndromes: stunning, hibernation and preconditioning. In every case it should be considered that ischemia is basically a metabolic problem, usually caused by coronary artery disease, stemming from lack of oxygen and blood flow. In principle, besides revascularization, metabolic therapy should be considered. In the past, metabolic therapies for effort angina have often been ignored. A current hypothesis is that the ischemic myocardium benefits from a switch from fatty acid to glucose metabolism. Two examples are (1) the hemodynamically neutral antianginal agent, trimetazidine, and (2) intravenous glucose-insulin-potassium (GIK). In acute myocardial infarction, GIK is undergoing a resurgence of interest due to the promising results of the large recent Argentinian trial. GIK acts in several ways, including the beneficial effects of insulin itself upon reperfusion, promotion of glycolysis, and inhibition of circulating fatty acids and hence of fatty acid oxidation. Metabolic therapy acting to protect the ischemic cell deserves more attention.