title: Influence of dichloroacetate on pulmonary gas exchange and ventilation during incremental exercise in healthy humans.
abstract: 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 (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+/-0.2mM; P<0.05) and throughout exercise until 630s (P<0.05). Blood [HCO(3)(-)] 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 CO(2) output. However, the reduced blood lactate accumulation during sub-maximal exercise with DCA did not enhance exercise tolerance.
authors.affiliation: School of Sport and Health Sciences, St. Luke's Campus, University of Exeter, Exeter, Devon, UK.
authors.forename: Daryl P
authors.initials: DP
authors.lastname: Wilkerson
authors.forename: Iain T
authors.initials: IT
authors.lastname: Campbell
authors.forename: Jamie R
authors.initials: JR
authors.lastname: Blackwell
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Berger
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jones
mesh_terms: D000328:Adult; D001639:Bicarbonates / Q000097:blood; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D001639:Bicarbonates; D019344:Lactic Acid; D003999:Dichloroacetic Acid