Comparison of sodium bicarbonate with dichloroacetate treatment of hyperlactatemia and lactic acidosis in the ischemic rat

Serum lactic acidosis is characterized by a pH less than 7.25 and lactate greater than 5 mEq. Although sodium bicarbonate (NaHCO3) is standard treatment for this condition, clinical and experimental studies suggest that high doses of NaHCO3 may be ineffectual or even detrimental to brain, cardiovascular, and respiratory function, as well as survival. For this reason, low dose therapy with NaHCO3 has been recommended. Sodium dichloroacetate (NaDCA) has been used successfully to treat clinical and experimentally-induced lactic acidosis. The present study was designed to compare the effects of low dose NaHCO3 with NaDCA on blood pressure, blood chemistries and brain metabolites in rats with a low flow-induced (Type A, the most common type) lactic acidosis. Fasted male Wistar rats were subjected to cerebral ischemia and systemic hypotension for 30 min at which time, if the pH or HCO-3 fell to 7.2 or 10, respectively, the rat was treated with NaHCO3, NaDCA, or an equal volume of sterile water. Over the 30 min of recirculation that followed ischemia, treatment had no effect on blood pressure or glucose or on brain glucose or glycogen. NaHCO3 had no effect on lactate but appeared to stabilize pH and increase HCO3- more than in sham- or NaDCA-treated rats. Although NaDCA caused a greater increase in HCO3- than sham treatment, pH continued to decline. However, lactate decreased more in NaDCA- than in sham- or NaHCO3- treated rats. These results suggest that low dose NaHCO3 is not detrimental in this model; however, although NaHCO3 stabilized pH, it did not rapidly correct the acidosis. NaDCA at this dose had no effect on the acidosis but was effective in decreasing lactate. Since serum lactate has previously correlated with survival and since higher doses of NaDCA have corrected lactic acidosis in other studies, future evaluation of postischemic treatment with higher doses of NaDCA is warranted.