DICHLOROACETATE STIMULATES CARBOHYDRATE-METABOLISM BUT DOES NOT IMPROVE SYSTOLIC FUNCTION IN ISCHEMIC PIG-HEART

Increased carbohydrate utilization may protect the heart during ischem ia and reperfusion. Dichloroacetate (DCA) stimulates pyruvate dehydrog enase, which is the rate-limiting step in oxidation of lactate and pyr uvate. The purpose of this study was to determine if the myocardial me tabolic changes induced by intracoronary DCA during myocardial ischemi a were accompanied by improvement in systolic function. A perfusion ci rcuit was created from the carotid to left anterior descending coronar y artery (LAD) in 11 anesthetized Yorkshire swine. Data were obtained under strict hemodynamic control at baseline, after 15 min of moderate (30%) LAD flow reduction, and after an additional 15 min of ischemia with either intracoronary DCA (3 mM, n = 6) or saline (n = 5) infusion . DCA decreased lactate release and increased lactate uptake during is chemia as measured by glucose and lactate carbon-labeled tracers. Desp ite these metabolic changes, no improvement in systolic shortening, mi crosphere blood flow, or oxygen consumption occurred. Thus, although D CA stimulated carbohydrate metabolism during myocardial ischemia, it d id not directly improve systolic function.