Dichloroacetate reduces plasma lactate levels but does not reduce infarct size in rabbit myocardium.
Dichloroacetate (DCA), an activator of pyruvate dehydrogenase (PDHC), enhances postischemic mechanical recovery of isolated hearts. It is not known whether this is secondary to reduced infarction or preservation of contractile function in viable cardiomyocytes. This study investigated the effect of DCA on myocardial infarct size. Anesthetized open chest rabbits underwent regional coronary occlusion and reperfusion. DCA (300 mg/kg plus 150 mg/kg 1 h later) was administered intravenously either before occlusion (DCA-O; n = 8) or at reperfusion (DCA-R; n = 7). Control rabbits (n = 8) received saline vehicle. Myocardial PDHC activity was measured after administration of 300 mg/kg i.v. DCA in 10 separate rabbits. DCA reduced plasma lactate levels and increased PDHC activity by 76%, from 2.79 +/- .30 mumol/min.g-1 to 4.92 +/- .44 mumol/min.g-1 (p < .005). However, infarct size in DCA-treated animals was not significantly different from Control (60 +/- 5% DCA-O, 57 +/- 6% DCA-R, 58 +/- 7% Control). We conclude that stimulation of pyruvate dehydrogenase does not limit infarct size.
Haessler
R
R
Department of Anesthesiology, Oregon Health Sciences University, Portland 97201, USA.
Davis
R F
RF
Wolff
R A
RA
Kozume
K
K
Shangraw
R
R
Van Winkle
D M
DM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000097:blood / Q000494:pharmacology*; D004789:Enzyme Activation; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011768:Pyruvate Dehydrogenase Complex / Q000819:agonists*; D011817:Rabbits
D001786:Blood Glucose; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid