Hyperpolarized <sup>13</sup>C 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 <sup>13</sup>C NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation. Methods Metabolism of hyperpolarized [1-<sup>13</sup>C]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1-<sup>13</sup>C]pyruvate. The hyperpolarized <sup>13</sup>C NMR results were corroborated with <sup>1</sup>H NMR spectroscopy of tissue extracts. Results Addition of isoproterenol to hearts after equilibration of hyperpolarized [1-<sup>13</sup>C]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1-<sup>13</sup>C]lactate signal within seconds after exposure to drug. The hyperpolarized H<sup>13</sup>CO<inf>3</inf><sup>-</sup> and hyperpolarized [1-<sup>13</sup>C]alanine signals were not affected by the isoproterenol-induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1-<sup>13</sup>C]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 <sup>13</sup>C 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

    Fingerprint

Keywords

  • imaging
  • isoproterenol
  • magnetic resonance spectroscopy
  • metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this