Effects of dichloroacetate on Vo2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans

Traditional control theories of muscle O-2 consumption 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. O-2 uptake ((V) over dot O-2) was measured breath by breath ( by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [P-i], [ATP], and pH (by P-31-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant ( tau) of either (V) over dot O-2 increase or PCr breakdown [tau(V) over dot O-2 45.5 +/- 7.9 vs. 44.3 +/- 8.2 s (means +/- SD; control vs. DCA); tauPCr 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 [P-i] ( - 1.7 +/- 2.1 mM); 2) the amplitude of the fundamental components for [ PCr] ( - 1.9 +/- 1.6 mM) and (V) over dot O-2 (-0.1 +/- 0.07 l/min, or 8%); and 3) the amplitude of the (V) over dot O-2 slow 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 tau(V) over dot O-2 or tau[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.