Facilitating postischemic reduction of cerebral lactate in rats.
OBJECTIVE
Dichloroacetate facilitates a decrease in brain lactate during reperfusion after incomplete ischemia. This study examined the possible activation of pyruvate dehydrogenase enzyme by dichloroacetate to explain this effect. Because the duration of ischemia and hyperglycemia exacerbate ischemic brain damage, the effect of both of these factors on lactate reduction with and without dichloroacetate treatment after ischemia also was explored.


METHODS
The two-vessel occlusion and controlled blood loss model of stroke was applied to anesthetized rats. Samples of cerebral cortex were analyzed for lactate by enzyme fluorometry and for pyruvate dehydrogenase activity by radioassay.


RESULTS
Treatment with dichloroacetate produced no significant stimulation of pyruvate dehydrogenase after ischemia. When the duration of ischemia was increased or 50% glucose was infused before ischemia, brain lactate was significantly higher (p less than 0.01, Duncan's test). After 30 minutes of ischemia, treatment with a low dose of dichloroacetate (25 mg/kg) improved the reduction in lactate (p less than 0.01, Duncan's test).


CONCLUSIONS
These results indicate that although dichloroacetate reduces brain lactate after cerebral ischemia, the mechanism of action does not involve dichloroacetate's known ability to stimulate pyruvate dehydrogenase. However, these data support the use of dichloroacetate to lower cerebral lactate, especially in cases where ischemia is greater than or equal to 30 minutes in duration. They also suggest that early restoration and maintenance of perfusion after ischemia and discontinuing the use of 50% glucose before impending ischemia likewise would facilitate reduction of postischemic brain lactate.
Dimlich
R V
RV
Department of Emergency Medicine, College of Medicine, University of Cincinnati, OH 45267-0769.
Nielsen
M M
MM
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003999:Dichloroacetic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid