Influence of dichloroacetate on pulmonary gas exchange and ventilation during incremental exercise in healthy humans

We hypothesised that dichloroacetate (DCA) would reduce blood lactate accumulation, pulmonary carbon dioxide output (V˙CO2) and ventilation (V˙E) at sub-maximal work rates, and improve exercise tolerance during incremental exercise in healthy humans. Nine males (mean±SD, age 27±4 years) completed, in random order, two ramp incremental cycle ergometer tests to the limit of tolerance following the intravenous infusion of DCA (75mg/kg body mass in 80ml saline) or an equivalent volume of saline (as placebo). Relative to control, blood [lactate] was significantly reduced by DCA immediately before exercise (CON: 0.7±0.2 vs. DCA: 0.5±0.2mM; P<0.05) and throughout exercise until 630s (P<0.05). Blood [HCO3−] was significantly higher in the DCA condition from 360s until 720s of exercise (P<0.05). V˙CO2 and V˙E were both lower throughout exercise in the DCA condition, with the differences reaching significance at 90 and 180s for V˙CO2 (P<0.05) and at 90, 180, 450, 540, 630, and 810s for V˙E (P<0.05). Exercise tolerance was not significantly altered (CON: 1029±109 vs. DCA: 1045±101s). Infusion of DCA resulted in reductions in blood [lactate], V˙CO2 and V˙E during sub-maximal incremental exercise, consistent with the existence of a link between the bicarbonate buffering of metabolic acidosis and increased CO2 output. However, the reduced blood lactate accumulation during sub-maximal exercise with DCA did not enhance exercise tolerance.