TY - JOUR
T1 - Dichloroacetate reduces plasma lactate levels but does not reduce infarct size in rabbit myocardium
AU - Haessler, Reinhard
AU - Davis, Richard F.
AU - Wolff, Roger A.
AU - Kuzume, Koh
AU - Shangraw, Robert
AU - Van Winkle, Donna M.
PY - 1996
Y1 - 1996
N2 - 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 μmol/minK·g-1 to 4.92 ± .44 μmol/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.
AB - 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 μmol/minK·g-1 to 4.92 ± .44 μmol/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.
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U2 - 10.1097/00024382-199601000-00013
DO - 10.1097/00024382-199601000-00013
M3 - Article
C2 - 8821106
AN - SCOPUS:0029684002
SN - 1073-2322
VL - 5
SP - 66
EP - 71
JO - Shock
JF - Shock
IS - 1
ER -