Dichloroacetate does not speed phase-II pulmonary VO2 kinetics following the onset of heavy intensity cycle exercise.
We hypothesised that pharmacological activation of the pyruvate dehydrogenase enzyme complex (PDC) by dichloroacetate (DCA) would speed phase-II pulmonary O2 uptake (VO2) kinetics following the onset of high-intensity, sub-maximal exercise. Eight healthy males (aged 19-33 years) completed two "square-wave" transitions of 6 min duration from unloaded cycling to a work-rate equivalent to approximately 80% of peak VO2 either with or without prior i.v. infusion of DCA (50 mg kg(-1) body mass in 50 ml saline). Pulmonary VO2 was measured breath-by-breath throughout all tests, and VO2 kinetics were determined using non-linear regression techniques from the averaged individual response to each of the conditions. Infusion of DCA resulted in significantly lower blood [lactate] during the baseline cycling period (means+/-SEM: control 0.9+/-0.1, DCA 0.5+/-0.1 mM; P<0.01) consistent with successful activation of PDC. However, DCA had no discernible effect on the rate at which VO2 increased towards the initially anticipated steady state following the onset of exercise as reflected in the time constant of the fundamental VO2 response (control 26.7+/-4.1, DCA 27.7+/-2.8 s). These results indicate that the principal limitation to oxidative metabolism following the onset of high-intensity, sub-maximal cycle exercise lies downstream from PDC and/or that muscle O2 consumption is primarily under "feedback" control via the concentration of one or more of the reactants associated with ATP hydrolysis.
Jones
Andrew M
AM
Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager, ST7 2HL, United Kingdom. a.m.jones@mmu.ac.uk
Koppo
Katrien
K
Wilkerson
Daryl P
DP
Wilmshurst
Sally
S
Campbell
Iain T
IT
D000328:Adult; D003999:Dichloroacetic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D005080:Exercise Test / Q000379:methods*; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D005082:Physical Exertion / Q000187:drug effects* / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology
D003999:Dichloroacetic Acid