title: In vivo mouse cardiac hyperpolarized magnetic resonance spectroscopy.
abstract: BACKGROUND
  Alterations in cardiac metabolism accompany many diseases of the heart. The advent of cardiac hyperpolarized magnetic resonance spectroscopy (MRS), via dynamic nuclear polarization (DNP), has enabled a greater understanding of the in vivo metabolic changes that occur as a consequence of myocardial infarction, hypertrophy and diabetes. However, all cardiac studies performed to date have focused on rats and larger animals, whereas more information could be gained through the study of transgenic mouse models of heart disease. Translation from the rat to the mouse is challenging, due in part to the reduced heart size (1/10(th)) and the increased heart rate (50%) in the mouse compared to the rat.
  
  
  RESULTS
  In this study, we have investigated the in vivo metabolism of [1-(13)C]pyruvate in the mouse heart. To demonstrate the sensitivity of the method to detect alterations in pyruvate dehydrogenase (PDH) flux, two well characterised methods of PDH modulation were performed; overnight fasting and infusion of sodium dichloroacetate (DCA). Fasting resulted in an 85% reduction in PDH flux, whilst DCA infusion increased PDH flux by 123%. A comparison of three commonly used control mouse strains was performed revealing significant metabolic differences between strains.
  
  
  CONCLUSIONS
  We have successfully demonstrated a hyperpolarized DNP protocol to investigate in vivo alterations within the diseased mouse heart. This technique offers a significant advantage over existing in vitro techniques as it reduces animal numbers and decreases biological variability. Thus [1-(13)C]pyruvate can be used to provide an in vivo cardiac metabolic profile of transgenic mice.
authors: Cardiac Metabolism Research Group, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK. michael.dodd@dpag.ox.ac.uk
authors: Michael S
authors: MS
authors: Dodd
authors: Vicky
authors: V
authors: Ball
authors: Rosalind
authors: R
authors: Bray
authors: Houman
authors: H
authors: Ashrafian
authors: Hugh
authors: H
authors: Watkins
authors: Kieran
authors: K
authors: Clarke
authors: Damian J
authors: DJ
authors: Tyler
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D003999:Dichloroacetic Acid / Q000008:administration & dosage; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting / Q000378:metabolism; D007262:Infusions, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid