Treatment of Lactic Acidosis with Dichloroacetate in Dogs

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Abstract

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 NaHCO3, 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 NaHCO3. The infusion of DCA and NaHCO3, delivered equal amounts of volume and sodium, although the quantity of NaHCO3 infused (2.5 meq/kg per h) was insufficient to normalize arterial pH.

Authors

Robert Park, Allen I. Arieff, William Leach, Virginia C. Lazarowitz