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Dichloroacetate reduces plasma lactate levels but does not reduce infarct size in rabbit myocardium
R Haessler1, R F Davis, R A Wolff
1Department of Anesthesiology, Oregon Health Sciences University, Portland 97201, USA.
Insights
Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDHC) but does not reduce myocardial infarct size in rabbits. This suggests PDHC activation alone does not limit heart damage after ischemia.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Ischemic Heart Disease
Background:
- Dichloroacetate (DCA) is known to activate pyruvate dehydrogenase (PDHC).
- DCA enhances postischemic mechanical recovery in isolated hearts, but the mechanism is unclear.
- It remains unknown if DCA reduces myocardial infarct size or preserves contractile function.
Purpose of the Study:
- To investigate the effect of DCA on myocardial infarct size in a rabbit model.
- To determine if DCA-induced PDHC activation limits infarct size following ischemia-reperfusion injury.
Main Methods:
- Anesthetized rabbits underwent regional coronary artery occlusion and reperfusion.
- DCA was administered intravenously either before occlusion or at reperfusion.
- Myocardial PDHC activity and infarct size were measured. Plasma lactate levels were also assessed.
Main Results:
- DCA administration significantly increased myocardial PDHC activity by 76%.
- DCA reduced plasma lactate levels.
- No significant difference in infarct size was observed between DCA-treated groups and the control group.
Conclusions:
- Stimulation of pyruvate dehydrogenase (PDHC) by DCA does not limit myocardial infarct size.
- The beneficial effects of DCA on cardiac recovery may not be mediated by infarct size reduction.
Abstract:
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.