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 (over(V, ̇)_{C O2}) and ventilation (over(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 (75 mg/kg body mass in 80 ml 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 ± 0.2 mM; P < 0.05) and throughout exercise until 630 s (P < 0.05). Blood [HCO₃ ^-] was significantly higher in the DCA condition from 360 s until 720 s of exercise (P < 0.05). over(V, ̇)_{C O2} and over(V, ̇)_E were both lower throughout exercise in the DCA condition, with the differences reaching significance at 90 and 180 s for over(V, ̇)_{C O2} (P < 0.05) and at 90, 180, 450, 540, 630, and 810 s for over(V, ̇)_E (P < 0.05). Exercise tolerance was not significantly altered (CON: 1029 ± 109 vs. DCA: 1045 ± 101 s). Infusion of DCA resulted in reductions in blood [lactate], over(V, ̇)_{C O2} and over(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.