Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate

The aim of the present study was to determine whether the activation of the pyruvate dehydrogenase complex (PDC) by dichloroacetate (DCA) is associated with faster O-2 uptake ((V)over dot O-2) on-kinetics was determined in isolated canine gastrocnemius muscles in situ (n = 6) during the transition from rest to 4 min of electrically stimulated isometric tetanic contractions, corresponding to similar to60-70% of peak (V)over dot O-2. Two conditions were compared: (1) control (saline infusion, C); and (2) DCA infusion (300 mg (kg body mass)(-1), 45 min before contraction). Muscle blood flow (Q) was measured continuously in the popliteal vein; arterial and popliteal vein O-2 contents were measured at rest and at 5-7 s intervals during the transition. Muscle (V)over dot O-2 was calculated as (Q)over dot multiplied by the arteriovenous O-2 content difference. Muscle biopsies were taken before and at the end of contraction for determination of muscle metabolite concentrations. DCA activated PDC at rest, as shown by the 9-fold higher acetylcarnitine concentration in DCA (vs. C; P < 0.0001). Phosphocreatine degradation and muscle lactate accumulation were not significantly different between C and DCA. DCA was associated with significantly less muscle fatigue. Resting and steady-state (V)over dot O-2 values during contraction were not significantly different between C and D CA. The time to reach 63% of the (V)over dot O-2 difference between the resting baseline and the steady-state lot values during contraction was 22.3 +/- 0.5 s in C and 24.5 +/- 1.4 s in DCA (n.s.). In this experimental model, activation of PDC by DCA resulted in a stockpiling of acetyl groups at rest and less muscle fatigue, but it did not affect 'anaerobic' energy provision and (V)over dot O-2 on-kinetics.