Competition of pyruvate with physiological substrates for oxidation by the heart: implications for studies with hyperpolarized [1-13C]pyruvate

Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1556-64. doi: 10.1152/ajpheart.00656.2009. Epub 2010 Mar 5.


Carbon 13 nuclear magnetic resonance (NMR) isotopomer analysis was used to measure the rates of oxidation of long-chain fatty acids, ketones, and pyruvate to determine the minimum pyruvate concentration ([pyruvate]) needed to suppress oxidation of these alternative substrates. Substrate mixtures were chosen to represent either the fed or fasted state. At physiological [pyruvate], fatty acids and ketones supplied the overwhelming majority of acetyl-CoA. Under conditions mimicking the fed state, 3 mM pyruvate provided approximately 80% of acetyl-CoA, but under fasting conditions 6 mM pyruvate contributed only 33% of acetyl-CoA. Higher [pyruvate], 10-25 mM, was associated with transient reduced cardiac output, but overall hemodynamic performance was unchanged after equilibration. These observations suggested that 3-6 mM pyruvate in the coronary arteries would be an appropriate target for studies with hyperpolarized [1-(13)C]pyruvate. However, the metabolic products of 3 mM hyperpolarized [1-(13)C]pyruvate could not be detected in the isolated heart during perfusion with a physiological mixture of substrates including 3% albumin. In the presence of albumin even at high concentrations of pyruvate, 20 mM, hyperpolarized H(13)CO(3)(-) could be detected only in the absence of competing substrates. Highly purified albumin (but not albumin from plasma) substantially reduced the longitudinal relaxation time of [1-(13)C]pyruvate. In conclusion, studies of cardiac metabolism using hyperpolarized [1-(13)C]pyruvate are sensitive to the effects of competing substrates on pyruvate oxidation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Albumins / pharmacology
  • Animals
  • Carbon Radioisotopes
  • Cardiac Output / physiology
  • Coronary Vessels / metabolism
  • Heart Function Tests
  • Hemodynamics / physiology
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Myocardium / metabolism*
  • Oxidation-Reduction
  • Oxygen Consumption / physiology
  • Pyruvic Acid / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Albumins
  • Carbon Radioisotopes
  • Acetyl Coenzyme A
  • Pyruvic Acid