Stroke, Vol 17, 525-528, Copyright © 1986 by American Heart Association
AR Colohan, FA Welsh, ED Miller and NF Kassell
Dichloroacetate (DCA) is known to prevent the phosphorylation of the
pyruvate dehydrogenase complex (PDHC) by blocking the action of PDH kinase.
This action allows the active PDHC to exert its effect on the metabolism of
glucose, lactate and alanine to acetyl CoA. DCA has been shown to reduce
serum lactate levels in humans and animals in such conditions as diabetes,
phenformin-induced hepatic failure, exercise, and endotoxin-induced shock.
Lactic acidosis in the brain has often been postulated as a cause of
neuronal damage following ischemia and hypoxia. Therefore, we examined the
effect of intravenously administered DCA (100 mg/kg) in rats that were
rendered hyperglycemic by intravenous glucose (2 g/kg), and then made to
undergo 15 minutes of incomplete cerebral ischemia by bilateral carotid
ligation and systemic hypotension (mean arterial pressure of 50 mm Hg). DCA
significantly reduced serum lactate levels pre-ischemia, but had no effect
on serum lactate levels after ischemia induction. Brain levels of lactate,
ATP and PCr after 15 minutes of incomplete ischemia were unaffected by DCA.
We conclude that in this in-vivo model the control of PDHC activity in the
brain may be different than that in the periphery, and that DCA was not
effective in reducing brain tissue lactate levels.
ARTICLES
The effect of dichloroacetate on brain lactate levels following incomplete ischemia in the hyperglycemic rat