THE EFFECTS OF DICHLOROACETATE ON LACTATE ACCUMULATION AND ENDURANCE IN AN EXERCISING RAT MODEL

Severe lactic acidosis usually accompanies intense endurance exercise. It has been postulated that glycogen depletion working in concert wit h elevated muscle and plasma lactate levels lead to a concomitant redu ction in pH. Their cumulative effect during prolonged physical exertio n now leads to muscular fatigue and eventually limit endurance capacit y. Therefore in the present study, dichloroacetate (DCA), a compound w hich enhances the rate of pyruvate oxidation thus reducing lactate for mation, has been evaluated in a validated rat model of sub-maximal exe rcise performance. Male rats (350 g) were divided into two groups (con trol-saline, IV and DCA 5 mg/kg, IV) and were exercised to exhaustion in a chamber (26 degrees C) on a treadmill (11 m/min, 6 degrees inclin e). When compared to controls, the DCA-treated rats had longer run tim es (169 vs 101 min) and a decreased heating rate (0.020 vs 0.029 degre es C/min). In addition, DCA attenuated the increase in plasma lactate (28 vs 40 mg/dl) and significantly reduced both the rate and absolute amount of depletion of muscle glycogen stores. These results suggest t hat the activation of pyruvate dehydrogenase activity by DCA resulted in a reduction in the rate of glycogenolysis in addition to decreasing lactate accumulation by presumably limiting the availability of pyruv ate for conversion to lactate, therefore increasing muscle carbohydrat e oxidation via the TCA cycle. Thus DCA effected a significant delay i n muscle fatigue.