Premium
Hyperpolarized 13 C NMR detects rapid drug‐induced changes in cardiac metabolism
Author(s) -
Khemtong Chalermchai,
Carpenter Nicholas R.,
Lumata Lloyd L.,
Merritt Matthew E.,
Moreno Karlos X.,
Kovacs Zoltan,
Malloy Craig R.,
Sherry A. Dean
Publication year - 2015
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.25419
Subject(s) - hyperpolarization (physics) , chemistry , metabolism , nuclear magnetic resonance spectroscopy , alanine , stimulation , glycogen , medicine , biochemistry , amino acid , organic chemistry
Purpose The diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized 13 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‐ 13 C]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1‐ 13 C]pyruvate. The hyperpolarized 13 C NMR results were corroborated with 1 H NMR spectroscopy of tissue extracts. Results Addition of isoproterenol to hearts after equilibration of hyperpolarized [1‐ 13 C]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1‐ 13 C]lactate signal within seconds after exposure to drug. The hyperpolarized H 13 CO 3 − and hyperpolarized [1‐ 13 C]alanine signals were not affected by the isoproterenol‐induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1‐ 13 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 13 C MRS may be useful for detecting abnormal glycogen metabolism in intact tissues. Magn Reson Med 74:312–319, 2015. © 2014 Wiley Periodicals, Inc.