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 O-2 uptake ((V)over dotO(2)) 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 similar to80% of peak (V)over dotO(2) either with or without prior i.v. infusion of DCA (50 mg kg(-1) body mass in 50 ml saline). Pulmonary (V)over dotO(2) was measured breath-by-breath throughout all tests, and (V)over dotO(2) 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 (V)over dotO(2) increased towards the initially anticipated steady state following the onset of exercise as reflected in the time constant of the fundamental (V)over dotO(2) 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 O-2 consumption is primarily under feedback control via the concentration of one or more of the reactants associated with ATP hydrolysis.