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

Karlos X. Moreno, Scott M. Sabelhaus, Matthew E. Merritt, A. Dean Sherry, Craig R. Malloy

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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 ∼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 [1-13C]pyruvate. "However, the metabolic products of 3 mM hyperpolarized [1-13C]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 H13CO3- 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 [1-13C]pyruvate. In conclusion, studies of cardiac metabolism using hyperpolarized [1-13C]pyruvate are sensitive to the effects of competing substrates on pyruvate oxidation.

Original languageEnglish (US)
Pages (from-to)H1556-H1564
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • Carbon-13
  • Dynamic nuclear polarization
  • Isolated rat heart
  • Myocardium
  • Nuclear magnetic resonance
  • Pyruvate
  • Substrate oxidation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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