Effects of dichloroacetate on V̇o2and intramuscular31P metabolite kinetics during high-intensity exercise in humans

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Abstract
Traditional control theories of muscle O2consumption are based on an “inertial” feedback system operating through features of the ATP splitting (e.g., [ADP] feedback, where brackets denote concentration). More recently, however, it has been suggested that feedforward mechanisms (with respect to ATP utilization) may play an important role by controlling the rate of substrate provision to the electron transport chain. This has been achieved by activation of the pyruvate dehydrogenase complex via dichloroacetate (DCA) infusion before exercise. To investigate these suggestions, six men performed repeated, high-intensity, constant-load quadriceps exercise in the bore of an magnetic resonance spectrometer with each of prior DCA or saline control intravenous infusions. O2uptake (V̇o2) was measured breath by breath (by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [Pi], [ATP], and pH (by31P-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant (τ) of either V̇o2increase or PCr breakdown [τV̇o245.5 ± 7.9 vs. 44.3 ± 8.2 s (means ± SD; control vs. DCA); τPCr 44.8 ± 6.6 vs. 46.4 ± 7.5 s; with 95% confidence intervals averaging < ±2 s]. DCA, however, resulted in significant ( P < 0.05) reductions in 1) end-exercise [lactate] (-1.0 ± 0.9 mM), intramuscular acidification (pH, +0.08 ± 0.06 units), and [Pi] (-1.7 ± 2.1 mM); 2) the amplitude of the fundamental components for [PCr] (-1.9 ± 1.6 mM) and V̇o2(-0.1 ± 0.07 l/min, or 8%); and 3) the amplitude of the V̇o2slow component. Thus, although the DCA infusion lessened the buildup of potential fatigue metabolites and reduced both the aerobic and anaerobic components of the energy transfer during exercise, it did not enhance either τV̇o2or τ[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.