DICHLOROACETATE AS METABOLIC THERAPY FOR MYOCARDIAL-ISCHEMIA AND FAILURE

This article critically reviews the pharmacologic effects of the inves tigational drug dichloroacetate (DCA), which activates the mitochondri al pyruvate dehydrogenase enzyme complex in cardiac tissue and thus pr eferentially facilitates aerobic oxidation of carbohydrate over fatty acids. The pharmacologic effects of DCA are compared with other interv entions, such as glucose plus insulin, inhibitors of long chain fatty acid oxidation and adenosine, that are also thought to exert their the rapeutic effects by altering myocardial energy metabolism. Short-term clinical and laboratory experiments demonstrate that intravenous DCA r apidly stimulates pyruvate dehydrogenase enzyme complex activity and, therefore, aerobic glucose oxidation in myocardial cells. Typically th ese effects are associated with suppression of myocardial long chain f atty acid metabolism and increased left ventricular stroke work and ca rdiac output without changes in coronary blood flow or myocardial oxyg en consumption. Although long-term studies are lacking, short-term par enteral administration of DCA appears to be safe and capable of signif icantly improving myocardial function in conditions of limited oxygen availability by increasing the efficient conversion of myocardial subs trate fuels into energy.