Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism

Chalermchai Khemtong, Nicholas R. Carpenter, Lloyd L. Lumata, Matthew E. Merritt, Karlos X. Moreno, Zoltan Kovacs, Craig R. Malloy, A. Dean Sherry

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Purpose The diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized 13C NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation. Methods Metabolism of hyperpolarized [1-13C]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1-13C]pyruvate. The hyperpolarized 13C NMR results were corroborated with 1H NMR spectroscopy of tissue extracts. Results Addition of isoproterenol to hearts after equilibration of hyperpolarized [1-13C]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1-13C]lactate signal within seconds after exposure to drug. The hyperpolarized H13CO3- and hyperpolarized [1-13C]alanine signals were not affected by the isoproterenol-induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1-13C]lactate signal that arises after stimulation by isoproterenol reflects a sudden increase in total tissue lactate derived from glycogen. Conclusion These results suggest that hyperpolarized pyruvate and 13C MRS may be useful for detecting abnormal glycogen metabolism in intact tissues. Magn Reson Med 74:312-319, 2015.

Original languageEnglish (US)
Pages (from-to)312-319
Number of pages8
JournalMagnetic resonance in medicine
Volume74
Issue number2
DOIs
StatePublished - Aug 1 2015

Keywords

  • imaging
  • isoproterenol
  • magnetic resonance spectroscopy
  • metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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