Graf H, Leach W, Arieff A I
J Clin Invest. 1985 Sep;76(3):919-23. doi: 10.1172/JCI112090.
The metabolic and systemic effects of dichloroacetate (DCA) in the treatment of hypoxic lactic acidosis were evaluated in the dog and compared with the infusion of equal quantities of volume and sodium. Hypoxic lactic acidosis was induced by ventilating dogs with an hypoxic gas mixture of 8% oxygen and 92% nitrogen, resulting in arterial PO2 of less than 30 mmHg, pH below 7.20, bicarbonate less than 15 mM, and lactate greater than 7 mM. After, the development of hypoxic lactic acidosis dogs were treated for 60 min with either DCA as sodium salt or NaCl at equal infusions of volume and sodium. Dogs treated with DCA showed a significant increase of arterial blood pH and bicarbonate, and steady levels of lactate, whereas NaCl resulted in further declines of blood pH and bicarbonate, and rising blood lactate levels. Overall lactate production decreased during therapy with either regimen, but hepatic lactate extraction increased significantly with DCA, while it remained unchanged with NaCl. Tissue lactate levels in liver and skeletal muscle decreased significantly with DCA treatment but were unchanged with NaCl. Additionally, an increase in muscle intracellular pH was observed only in DCA treated dogs. A possible mechanism for the observed actions of DCA might be related to a significant increase in oxygen delivery to tissues. Such an effect was found with DCA administration, but was not observed with NaCl therapy. In conclusion, DCA therapy in hypoxic lactic acidosis has beneficial systemic effects compared with therapy with NaCl. DCA administration is accompanied by increases of blood pH and bicarbonate, a decrease in lactate production, and enhanced liver lactate extraction, and a lowering of tissue lactate levels.
在犬类动物中评估了二氯乙酸（DCA）治疗低氧性乳酸性酸中毒的代谢及全身效应，并与输注等量体积和钠的情况进行了比较。通过用含8%氧气和92%氮气的低氧混合气体对犬进行通气来诱导低氧性乳酸性酸中毒，导致动脉血氧分压低于30 mmHg、pH低于7.20、碳酸氢盐低于15 mM且乳酸高于7 mM。在低氧性乳酸性酸中毒发生后，用DCA钠盐或氯化钠以等量体积和钠进行输注，对犬治疗60分钟。用DCA治疗的犬动脉血pH和碳酸氢盐显著升高，乳酸水平稳定，而氯化钠导致血pH和碳酸氢盐进一步下降，血乳酸水平上升。两种治疗方案在治疗期间总体乳酸生成均减少，但DCA治疗时肝脏乳酸摄取显著增加，而氯化钠治疗时则保持不变。DCA治疗使肝脏和骨骼肌组织乳酸水平显著降低，而氯化钠治疗则无变化。此外，仅在接受DCA治疗的犬中观察到肌肉细胞内pH升高。DCA所观察到的作用的一种可能机制可能与组织氧输送显著增加有关。DCA给药时发现了这种效应，但氯化钠治疗时未观察到。总之，与氯化钠治疗相比，DCA治疗低氧性乳酸性酸中毒具有有益的全身效应。DCA给药伴随着血pH和碳酸氢盐升高、乳酸生成减少、肝脏乳酸摄取增强以及组织乳酸水平降低。
