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).


CONCLUSIONS
In acute limb ischemia and reperfusion, DCA administration provides metabolic protection to skeletal muscle.
Platz
Timothy A
TA
Department of Vascular and Endovascular Surgery, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708, USA.
Wilson
Jeffrey S
JS
Kline
Jeffrey A
JA
Rushing
Greg
G
Parker
Jaime L
JL
Moore
Erin M
EM
Southern
Fredrick N
FN
D000208:Acute Disease; D000255:Adenosine Triphosphate; D000818:Animals; D000868:Anterior Compartment Syndrome / Q000150:complications / Q000188:drug therapy*; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy*; D018763:Muscle Fatigue / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D009336:Necrosis; D010807:Physical Endurance; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid