Effect of dichloroacetate on plasma lactic acid in exercising dogs

Dichloroacetate sodium (DCA) has been shown to reduce circulating levels of lactic acid (LA) under a variety of experimental and clinical conditions. We have examined the effect of DCA on the lactacidemia of exercise in treadmill-exercised dogs. One group of animals (n = 8) was tested at light, moderate, and heavy exercise work loads. Plasma LA, 19 +/- 2mg/dl at rest, increased to 26 +/- 4, 38 +/- 5, and 52 +/- 6 mg/dl during the three workloads, respectively. In the same animals, when identical treadmill tests were conducted after DCA (100 mg/kg, iv), the rise in LA was significantly attenuated. Lactic acid values were 11 +/- 2 mg/dl at rest after DCA and 15 +/- 2, 20 +/- 4, and 23 +/- 3 mg/dl for the light, moderate, and heavy workloads, respectively. Another group of dogs (n = 6) performed prolonged moderate exercise. Under untreated conditions, LA increased from 24 +/- 1 mg/dl at rest, to 41 +/- 6 mg/dl at 10 min, and 50 +/- 5 mg/dl at 50 min. During repeat tests, DCA was given at 12 min when LA was 30 +/- 6 mg/dl. At 50 min, LA was 18 +/- 3 mg/dl or 60% lower than that observed during the untreated run. Because DCA has been shown to increase pyruvate dehydrogenase enzyme activity, these data suggest that this enzyme may be an important factor in LA metabolism during exercise.