Park R, Arieff A I
J Clin Invest. 1982 Oct;70(4):853-62. doi: 10.1172/jci110682.
Lactic acidosis is a clinical condition due to accumulation of H(+) ions from lactic acid, characterized by blood lactate levels >5 mM and arterial pH <7.25. In addition to supportive care, treatment usually consists of intravenous NaHCO(3), with a resultant mortality >60%. Dichloroacetate (DCA) is a compound that lowers blood lactate levels under various conditions in both man and laboratory animals. It acts to increase pyruvate oxidation by activation of pyruvate dehydrogenase. We evaluated the effects of DCA in the treatment of two different models of type B experimental lactic acidosis in diabetic dogs: hepatectomy-lactic acidosis and phenformin-lactic acidosis. The metabolic and systemic effects examined included arterial blood pH and levels of bicarbonate and lactate; the intracellular pH (pHi) in liver and skeletal muscle; cardiac index, arterial blood pressure and liver blood flow; liver lactate uptake and extrahepatic splanchnic (gut) lactate production; and mortality. Effects of DCA were compared with those of either NaCl or NaHCO(3). The infusion of DCA and NaHCO(3), delivered equal amounts of volume and sodium, although the quantity of NaHCO(3) infused (2.5 meq/kg per h) was insufficient to normalize arterial pH. In phenformin-lactic acidosis, DCA-treated animals had a mortality of 22%, vs. 89% in those treated with NaHCO(3). DCA therapy increased arterial pH and bicarbonate, liver pHi and cardiac index, with increased liver lactate uptake and a fall in blood lactate. With NaHCO(3) therapy, there were decrements of cardiac index and liver pHi, with an increase in venous pCO(2) and gut production of lactate. Dogs with hepatectomy-lactic acidosis were either treated or pretreated with DCA. Treatment with DCA resulted in stabilization of cardiac index, a fall in blood lactate, and 17% mortality. NaHCO(3) was associated with a continuous decline of cardiac index, rise in blood lactate, and 67% mortality. In dogs pretreated with NaCl, mortality was 33%, but all dogs pretreated with DCA survived. Dogs pretreated with DCA also had lower blood lactate and higher arterial pH and bicarbonate than did those pretreated with NaCl.Thus, in either of two models of type B experimental lactic acidosis, treatment with DCA improves cardiac index, arterial pH, bicarbonate and lactate, and liver pHi. The mortality in dogs with type B lactic acidosis was significantly less in DCA-treated animals than in those treated with other modalities.
乳酸酸中毒是一种由于乳酸中H⁺离子蓄积所致的临床病症，其特征为血乳酸水平>5 mM且动脉血pH<7.25。除支持治疗外，治疗通常包括静脉输注NaHCO₃，死亡率>60%。二氯乙酸（DCA）是一种在人和实验动物的各种情况下均能降低血乳酸水平的化合物。它通过激活丙酮酸脱氢酶来增加丙酮酸氧化。我们评估了DCA对糖尿病犬B型实验性乳酸酸中毒的两种不同模型（肝切除 - 乳酸酸中毒和苯乙双胍 - 乳酸酸中毒）的治疗效果。所检测的代谢和全身效应包括动脉血pH、碳酸氢盐和乳酸水平；肝脏和骨骼肌中的细胞内pH（pHi）；心脏指数、动脉血压和肝血流量；肝脏乳酸摄取和肝外内脏（肠道）乳酸生成；以及死亡率。将DCA的效果与NaCl或NaHCO₃的效果进行比较。输注DCA和NaHCO₃的量和钠含量相等，尽管输注的NaHCO₃量（2.5 meq/kg每小时）不足以使动脉血pH正常化。在苯乙双胍 - 乳酸酸中毒中，接受DCA治疗的动物死亡率为22%，而接受NaHCO₃治疗的动物死亡率为89%。DCA治疗可提高动脉血pH和碳酸氢盐水平、肝脏pHi和心脏指数，增加肝脏乳酸摄取并降低血乳酸水平。使用NaHCO₃治疗时，心脏指数和肝脏pHi下降，静脉血pCO₂升高且肠道乳酸生成增加。肝切除 - 乳酸酸中毒的犬接受DCA治疗或预处理。DCA治疗可使心脏指数稳定、血乳酸下降，死亡率为17%。NaHCO₃治疗则导致心脏指数持续下降、血乳酸升高，死亡率为67%。用NaCl预处理的犬死亡率为33%，但所有用DCA预处理的犬均存活。用DCA预处理的犬血乳酸水平也低于用NaCl预处理的犬，且动脉血pH和碳酸氢盐水平更高。因此，在B型实验性乳酸酸中毒的两种模型中，DCA治疗均可改善心脏指数、动脉血pH、碳酸氢盐和乳酸水平以及肝脏pHi。B型乳酸酸中毒犬接受DCA治疗后的死亡率显著低于接受其他治疗方式的犬。
