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Myocardial energy metabolism : a therapeutic target in cardiac ischemia. B.S. Kalra and V. Roy. Efficacy of metabolic modulators in ischemic heart disease: an overview. J Clin Pharmacol. 2011. Published online 7 March 2011.
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Myocardialenergymetabolism: a therapeutictarget in cardiacischemia B.S. Kalra and V. Roy. Efficacy of metabolic modulators in ischemic heart disease: an overview. J Clin Pharmacol. 2011.Published online 7 March 2011. H. Tuunanen and J. Knuuti. Metabolic remodelling in human heart failure. Cardiovasc Res. 2011. Advance online access published March 3, 2011.
Energy: a vital need for the heart Each day, the heart beats about 100 000 times and pumps approximately 10 metric tonnes of blood through the body. • Cardiac muscle uses 1 mM ATP per second • Energy reserves: 20mM of Pi (ATP and PCr) • >90% of energy is produced as PCr • >90% energy comes from mitochondrial respiration • During intense exercise the heart uses >90% of oxidative capacity
The heart mainly produces ATP through oxidative pathways • Fatty Acid -oxidation • Provides 60% to 90% of energy. • Requires more 02 than glucose. • ATP/02=2.6 • Glucose oxidation • Provides 10% to 40% of energy. • More 02 efficientpathway. • ATP/02=3 Fattyacids Glucose Acyl coA Pyruvate Acetyl coA Energy (ATP)
Fatty acid oxidation Anaerobic glycolysis Cardiac disease is closely linked to impairments in cardiac energy metabolism Fattyacids Glucose Acyl coA Pyruvate Acetyl coA Cell acidosis Calcium overload Cell damage • Increase need of ATP for homeostasis. Energy (ATP) Contractile dysfunction
Therapeutic perspectives for agents modulating cardiac energy metabolism HeartMetab. 2008;38:5-14,