Durkot M J, De Garavilla L, Caretti D, Francesconi R
U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA.
Int J Sports Med. 1995 Apr;16(3):167-71. doi: 10.1055/s-2007-972986.
Severe lactic acidosis usually accompanies intense endurance exercise. It has been postulated that glycogen depletion working in concert with elevated muscle and plasma lactate levels lead to a concomitant reduction in pH. Their cumulative effect during prolonged physical exertion now leads to muscular fatigue and eventually limit endurance capacity. Therefore in the present study, dichloroacetate (DCA), a compound which enhances the rate of pyruvate oxidation thus reducing lactate formation, has been evaluated in a validated rat model of sub-maximal exercise performance. Male rats (350 g) were divided into two groups (control-saline, i.v. and DCA 5 mg/kg, i.v.) and were exercised to exhaustion in a chamber (26 degrees C) on a treadmill (11 m/min, 6 degrees incline). When compared to controls, the DCA-treated rats had longer run times (169 vs 101 min) and a decreased heating rate (0.020 vs 0.029 degrees 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 that 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 pyruvate for conversion to lactate, therefore increasing muscle carbohydrate oxidation via the TCA cycle. Thus DCA effected a significant delay in muscle fatigue.
严重乳酸酸中毒通常伴随高强度耐力运动。据推测，糖原耗竭与升高的肌肉和血浆乳酸水平共同作用导致pH值随之降低。它们在长时间体力消耗过程中的累积效应现在导致肌肉疲劳并最终限制耐力。因此，在本研究中，二氯乙酸（DCA），一种能提高丙酮酸氧化速率从而减少乳酸生成的化合物，已在一个经过验证的次最大运动表现大鼠模型中进行了评估。雄性大鼠（350克）被分为两组（对照组 - 静脉注射生理盐水和DCA 5毫克/千克，静脉注射），并在一个房间（26摄氏度）的跑步机上（11米/分钟，6度倾斜）运动至疲惫。与对照组相比，接受DCA治疗的大鼠有更长的跑步时间（169对101分钟）和更低的升温速率（0.020对0.029摄氏度/分钟）。此外，DCA减轻了血浆乳酸的升高（28对40毫克/分升），并显著降低了肌肉糖原储备消耗的速率和绝对量。这些结果表明，DCA激活丙酮酸脱氢酶活性除了通过可能限制丙酮酸转化为乳酸的可用性来减少乳酸积累外，还导致糖原分解速率降低，因此通过三羧酸循环增加了肌肉碳水化合物氧化。因此，DCA显著延迟了肌肉疲劳。
