Effect of dichloroacetate on the exercise performance of patients with heart failure.
The reduced maximal exercise capacity of patients with heart failure has been attributed to skeletal muscle underperfusion with resultant intramuscular lactic acidosis and muscular fatigue. To investigate this hypothesis, the effect of dichloroacetate, a drug that decreases lactate formation by increasing pyruvate oxidation, on the maximal exercise performance of 18 patients with heart failure and reduced ejection fraction (25 +/- 9%) was examined. Exercise tests after parenteral dextrose (control) and dichloroacetate were performed 1 week apart. The sequence of interventions was randomized in a double-blind manner. Dichloroacetate decreased blood lactate at rest (control 8.0 +/- 2.5 versus dichloroacetate 5.6 +/- 2.9 mg/dl), throughout exercise and at peak exercise (control 26.0 +/- 14.3 versus dichloroacetate 19.4 +/- 10.8) (all p less than 0.05). In contrast, dichloroacetate had no effect on exercise time (control 15.2 +/- 6.0 versus dichloroacetate 15.9 +/- 6.2 min) or peak exercise oxygen consumption (control 1,280 +/- 498 ml/min versus dichloroacetate 1,312 +/- 530 ml/min) (both p = NS). In six subjects, dichloroacetate also had no effect at peak exercise on leg blood flow (control 2.8 +/- 1.1 versus dichloroacetate 3.0 +/- 0.6 liters/min) or femoral oxygen vein saturation (control 12.7 +/- 4.1% versus dichloroacetate 12.5 +/- 5.7%). These data suggest that intramuscular lactate accumulation is not responsible for muscular fatigue during exercise in patients with heart failure.
Wilson
J R
JR
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104.
Mancini
D M
DM
Ferraro
N
N
Egler
J
J
D000085:Acetates / Q000494:pharmacology*; D000140:Acidosis, Lactic / Q000150:complications; D000328:Adult; D000368:Aged; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D015444:Exercise; D005221:Fatigue / Q000209:etiology; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D010101:Oxygen Consumption; D012039:Regional Blood Flow / Q000187:drug effects
D000085:Acetates; D007773:Lactates; D019344:Lactic Acid; D003999:Dichloroacetic Acid