Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise

This study investigated whether hyperoxic breathing (100% O2) or increasing oxidative substrate supply [dichloroacetate (DCA) infusion] would increase oxidative phosphorylation and reduce the reliance on substrate phosphorylation at the onset of high-intensity aerobic exercise. Eight male subjects cycled at 90% maximal O2 uptake (Vo2max) for 90 s in three randomized conditions: 1) normoxic breathing and saline infusion over 1 h immediately before exercise (CON), 2) normoxic breathing and saline infusion with DCA (100 mg/kg body wt), and 3) hyperoxic breathing for 20 min at rest and during exercise and saline infusion (HYP). Muscle biopsies from the vastus lateralis were sampled at rest and after 30 and 90 s of exercise. DCA infusion increased pyruvate dehydrogenase (PDH) activation above CON and HYP (3.10 ± 0.23, 0.56 ± 0.08, 0.69 ± 0.05 mmol.kg wet muscle-1.min-1, respectively) and significantly increased both acetyl-CoA and acetylcarnitine (11.0 ± 0.7, 2.0 ± 0.5, 2.2 ± 0.5 mmol/kg dry muscle, respectively) at rest. However, DCA and HYP did not alter phosphocreatine degradation and lactate accumulation and, therefore, the reliance on substrate phosphorylation during 30 s (CON, 51.2 ± 5.4; DCA, 56.5 ± 7.1; HYP, 69.5 ± 6.3 mmol ATP/kg dry muscle) and 90 s of exercise (CON, 90.6 ± 9.5; DCA, 107.2 ± 13.0; HYP, 101.2 ± 15.2 mmol ATP/kg dry muscle). These data suggest that the rate of oxidative phosphorylation at the onset of exercise at 90% Vo2 max is not limited by oxygen availability to the active muscle or by substrate availability (metabolic inertia) at the level of PDH in aerobically trained subjects.