title: Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism.
abstract: OBJECTIVE
  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-(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 13C NMR results were corroborated with 1H 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)CO3 (-) 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.
  
  
  CONCLUSIONS
  These results suggest that hyperpolarized pyruvate and 13C MRS may be useful for detecting abnormal glycogen metabolism in intact tissues.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Chalermchai
authors.initials: C
authors.lastname: Khemtong
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Carpenter
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Lloyd L
authors.initials: LL
authors.lastname: Lumata
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Merritt
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Karlos X
authors.initials: KX
authors.lastname: Moreno
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|Department of Chemistry, University of Texas at Dallas, Richardson, Texas, USA.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D006003:Glycogen / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007553:Isotope Labeling; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D019289:Pyruvic Acid / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000318:Adrenergic beta-Agonists; D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D019344:Lactic Acid; D019289:Pyruvic Acid; D006003:Glycogen; D007545:Isoproterenol
keywords: imaging; isoproterenol; magnetic resonance spectroscopy; metabolism