Therapeutic benefit of dichloroacetate in experimentally induced hypoxic lactic acidosis

Although dichloroacetate (DCA) ameliorates type B lactic acidosis, its effectiveness in type A hypoxic lactic acidosis is uncertain on both theoretical and experimental grounds. Because this drug was reported recently to successfully ameliorate lactic acidosis in patients with type A lactic acidosis, we tested its effect on pure hypoxia-induced lactic acidosis in rats. Anesthetized, mechanically ventilated rats were subjected to a decrease in FiO2, from 21% to 7.5% over a 20-minute period, and maintenance of hypoxia for an additional hour. Either DCA (300 mg/kg) or equal volumes of normal saline solution or hypertonic saline solution was infused during the induction period. DCA significantly attenuated the rise in blood lactate levels in comparison with both control groups, and also resulted in maintenance of a higher blood pH and bicarbonate level. Systolic blood pressure was also maintained at a higher, although significantly subnormal level, in the DCA group. DCA increased urine flow rate and sodium excretion, and additional studies with the isolated perfused rat kidney suggested that this resulted in part from a direct drug-mediated effect on renal sodium handling. Although these results do not delineate the underlying mechanisms, they clearly demonstrate that DCA is an effective form of therapy for type A lactic acidosis.