Facilitating postischemic reduction of cerebral lactate in rats.

Abstract:

BACKGROUND AND PURPOSE: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.

journal_name

Stroke

journal_title

Stroke

authors

Dimlich RV,Nielsen MM

doi

10.1161/01.str.23.8.1145

subject

Has Abstract

pub_date

1992-08-01 00:00:00

pages

1145-52; discussion 1152-3

issue

8

eissn

0039-2499

issn

1524-4628

journal_volume

23

pub_type

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