Influence of DCA on Pulmonary &OV0312;O2 Kinetics during Moderate-Intensity Cycle Exercise

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Abstract
To test the hypothesis that pharmacological activation of the pyruvate dehydrogenase enzyme complex (PDC) with dichloroacetate (DCA) would speed phase II pulmonary oxygen uptake ((.-)V(O2)) kinetics after the onset of subsequent moderate-intensity (40-45% ((.-)V(O2)) peak) cycle exercise. Seven healthy males (mean +/- SD age 25 +/- 4 yr, body mass 75.3 +/- 9.4 kg) performed four "square-wave" transitions from unloaded cycling to a work rate requiring 90% of the predetermined gas exchange threshold either with or without prior infusion of DCA (50 mg x kg body mass in 50 mL saline). Pulmonary ((.-)V(O2)) was measured breath-by-breath in all tests and ((.-)V(O2)) kinetics were determined from the averaged individual response to each condition using nonlinear regression techniques. The blood [lactate] measured immediately before the onset of exercise was significantly reduced in the DCA condition (C: 1.1 +/- 0.3 vs DCA: 0.6 +/- 0.3 mM; P < 0.01) consistent with successful activation of the PDC. However, DCA had no discernible effect on the rate at which ((.-)V(O2)) increased toward the steady state after the onset of exercise as reflected in the phase II time constant (C: 28.5 +/- 11.8 vs DCA: 29.4 +/- 14.9 s). The results suggest that PDC activation does not represent a principal intramuscular limitation to ((.-)V(O2)) kinetics after the onset of moderate-intensity exercise.