Dichloroacetate improves postischemic function of hypertrophied rat hearts

Area of Science:

• Cardiovascular Physiology
• Metabolic Regulation
• Cardiac Hypertrophy

Background:

• Hypertrophied hearts exhibit greater postischemic dysfunction compared to non-hypertrophied hearts.
• This dysfunction is linked to reduced glucose oxidation and elevated glycolysis rates.

Purpose of the Study:

• To investigate if stimulating glucose oxidation during reperfusion improves postischemic recovery in hypertrophied hearts.
• To assess the role of dichloroacetate (DCA) in modulating cardiac metabolism and function.

Main Methods:

• Isolated working rat hearts (control and hypertrophied) underwent global ischemia followed by reperfusion.
• Dichloroacetate (DCA), a pyruvate dehydrogenase activator, was administered at reperfusion to stimulate glucose oxidation.
• Cardiac function, glycolysis, and glucose oxidation rates were measured.

Main Results:

• Untreated hypertrophied hearts showed higher glycolysis and lower glucose oxidation/function recovery.
• DCA significantly increased glucose oxidation and decreased glycolysis in hypertrophied hearts.
• DCA improved cardiac function in both control and hypertrophied hearts, normalizing recovery in the latter.

Conclusions:

• Dichloroacetate (DCA) normalizes postischemic function in hypertrophied rat hearts.
• DCA improves the metabolic coupling of glucose oxidation and glycolysis by increasing oxidation and decreasing glycolysis.
• Findings support the hypothesis that impaired glucose metabolism contributes to exaggerated postischemic dysfunction in hypertrophied hearts.