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

22 Citations (Scopus)

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

Pyruvic Acid
Isoproterenol
Lactic Acid
Pharmaceutical Preparations
Glycogen
Magnetic Resonance Spectroscopy
Tissue Extracts
Workload
Alanine
Adrenergic Agents
Myocardium
Carbon-13 Magnetic Resonance Spectroscopy

Keywords

  • imaging
  • isoproterenol
  • magnetic resonance spectroscopy
  • metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Hyperpolarized <sup>13</sup>C NMR detects rapid drug-induced changes in cardiac metabolism. / Khemtong, Chalermchai; Carpenter, Nicholas R.; Lumata, Lloyd L.; Merritt, Matthew E.; Moreno, Karlos X.; Kovacs, Zoltan; Malloy, Craig R.; Sherry, A. Dean.

In: Magnetic Resonance in Medicine, Vol. 74, No. 2, 01.08.2015, p. 312-319.

Research output: Contribution to journalArticle

Khemtong, Chalermchai ; Carpenter, Nicholas R. ; Lumata, Lloyd L. ; Merritt, Matthew E. ; Moreno, Karlos X. ; Kovacs, Zoltan ; Malloy, Craig R. ; Sherry, A. Dean. / Hyperpolarized <sup>13</sup>C NMR detects rapid drug-induced changes in cardiac metabolism. In: Magnetic Resonance in Medicine. 2015 ; Vol. 74, No. 2. pp. 312-319.
@article{091e5bdc1ed44e99a656b6f9992812de,
title = "Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism",
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.",
keywords = "imaging, isoproterenol, magnetic resonance spectroscopy, metabolism",
author = "Chalermchai Khemtong and Carpenter, {Nicholas R.} and Lumata, {Lloyd L.} and Merritt, {Matthew E.} and Moreno, {Karlos X.} and Zoltan Kovacs and Malloy, {Craig R.} and Sherry, {A. Dean}",
year = "2015",
month = "8",
day = "1",
doi = "10.1002/mrm.25419",
language = "English (US)",
volume = "74",
pages = "312--319",
journal = "Magnetic Resonance in Medicine",
issn = "0740-3194",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism

AU - Khemtong, Chalermchai

AU - Carpenter, Nicholas R.

AU - Lumata, Lloyd L.

AU - Merritt, Matthew E.

AU - Moreno, Karlos X.

AU - Kovacs, Zoltan

AU - Malloy, Craig R.

AU - Sherry, A. Dean

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

KW - imaging

KW - isoproterenol

KW - magnetic resonance spectroscopy

KW - metabolism

UR - http://www.scopus.com/inward/record.url?scp=84937714803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937714803&partnerID=8YFLogxK

U2 - 10.1002/mrm.25419

DO - 10.1002/mrm.25419

M3 - Article

VL - 74

SP - 312

EP - 319

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

SN - 0740-3194

IS - 2

ER -