IMPROVED HEMODYNAMIC FUNCTION AND MECHANICAL EFFICIENCY IN CONGESTIVE-HEART-FAILURE WITH SODIUM DICHLOROACETATE

Objectives. The purpose of this study was to determine whether sodium dichloroacetate improves hemodynamic performance and mechanical effici ency in congestive heart failure. Background. Congestive heart failure is associated with impaired hemodynamic performance and reduced mecha nical efficiency. Dichloroacetate stimulates pyruvate dehydrogenase ac tivity by inhibition of pyruvate dehydrogenase kinase, which results i n inhibition of free fatty acid metabolism and stimulation of high res piratory quotient glucose and lactate consumption by the heart. Facili tation of glucose and lactate consumption with dichloroacetate should improve mechanical efficiency of the failing ventricle. Methods. Ten p atients with New York Heart Association functional class III to TV con gestive heart failure were studied. Dichloroacetate (50 mg/kg body wei ght) was administered intravenously for 30 min, with measurements of h emodynamic variables, coronary sinus blood flow and blood gas, glucose and lactate levels far 2 h. The same patients were also given dobutam ine (5 to 12.5 mu g/kg per min) for comparison. Results. Therapeutic l evels of dichloroacetate were achieved (100 to 160 mu g/liter of plasm a). Myocardial consumption of lactate was stimulated from 29% to 37.4% . Forward stroke volumes increased (+5.3 ml/beat, p < 0.02), as did le ft ventricular stroke work (+1.8 g-m/m(2) per beat, p < 0.02) and left ventricular minute work (from 1.38 to 1.55 kg-m/m(2) per min, p < 0.0 1). Myocardial oxygen consumption decreased (from 19.3 to 16.5 ml/min, p = 0.06) as left ventricular minute work increased. Left ventricular mechanical efficiency thus improved from 15.2% to 20.6% (p = 0.03). D obutamine administration resulted in the opposite trend with respect t o myocardial lactate extraction (from 34% to 15.3%, p < 0.02). Stroke volume increased (+7.4 ml/beat, p = NS vs. dichloroacetate), as did le ft ventricular minute work (from 1.29 to 1.59 g-m/m(2) per min, p < 0. 01 vs. dichloroacetate) and myocardial oxygen consumption (from 18.6 t o 21.0 ml/min, p = 0.06 vs. dichloroacetate). Left ventricular mechani cal efficiency did not change with dobutamine administration (from 16. 4% to 15.8%, p = NS). Conclusions. Dichloroacetate administration stim ulates myocardial lactate consumption and improves left ventricular me chanical efficiency. Forward stroke volume and left ventricular minute work increase significantly, with a simultaneous reduction in myocard ial oxygen consumption. Dobutamine administration results in similar h emodynamic improvements but with no change in left ventricular mechani cal efficiency and with opposite effects on lactate metabolism. The op posing metabolic actions, yet similar hemodynamic responses, of dichlo roacetate and dobutamine suggest that these agents may be complementar y in the treatment of congestive heart failure.