The beneficial effects of dichloroacetate in acute limb ischemia.

Objective: The purpose of this study was to determine the effects of dichloroacetate (DCA) in acute limb ischemia.

Methods: Anterior tibialis muscle samples of DCA-treated and control animals (Sprague Dawley rats) were collected and assayed for pyruvate dehydrogenase activity, lactate, adenosine triphosphate, and creatine phosphate using spectrophotometry. A physiograph was used to measure fatigability. In an ischemia/reperfusion model using New Zealand rabbits, serum lactate and end-tidal CO2 were compared. Skeletal muscle was evaluated microscopically for muscle necrosis.

Results: DCA administration resulted in a 50% increase in pyruvate dehydrogenase activity (p = 0.025), reversal of the increase in lactate levels seen during acute limb ischemia (p = 0.41), a significant increase in the time to skeletal muscle fatigue (p = 0.05), a trend toward increased adenosine triphosphate (p = 0.07), and a significant increase in creatine phosphate (p < 0.02). DCA treatment resulted in a decrease in serum lactate (p < 0.01) and end-tidal CO2 (p < 0.001).

Conclusion: In acute limb ischemia and reperfusion, DCA administration provides metabolic protection to skeletal muscle.