title: In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart.
abstract: OBJECTIVE
  The aim of this work was to use hyperpolarized carbon-13 ((13)C) magnetic resonance (MR) spectroscopy and cine MR imaging (MRI) to assess in vivo cardiac metabolism and function in the 15-week-old spontaneously hypertensive rat (SHR) heart. At this time point, the SHR displays hypertension and concentric hypertrophy. One of the cellular adaptations to hypertrophy is a reduction in β-oxidation, and it has previously been shown that in response to hypertrophy the SHR heart switches to a glycolytic/glucose-oxidative phenotype.
  
  
  RESULTS
  Cine-MRI (magnetic resonance imaging) was used to assess cardiac function and degree of cardiac hypertrophy. Wistar rats were used as controls. SHRs displayed functional changes in stroke volume, heart rate, and late peak-diastolic filling alongside significant hypertrophy (a 56% increase in left ventricular mass). Using hyperpolarized [1-(13)C] and [2-(13)C]pyruvate, an 85% increase in (13)C label flux through pyruvate dehydrogenase (PDH) was seen in the SHR heart and (13)C label incorporation into citrate, acetylcarnitine, and glutamate pools was elevated in proportion to the increase in PDH flux. These findings were confirmed using biochemical analysis of PDH activity and protein expression of PDH regulatory enzymes.
  
  
  CONCLUSIONS
  Functional and structural alterations in the SHR heart are consistent with the hypertrophied phenotype. Our in vivo work indicates a preference for glucose metabolism in the SHR heart, a move away from predominantly fatty acid oxidative metabolism. Interestingly, (13)C label flux into lactate was unchanged, indicating no switch to an anaerobic glycolytic phenotype, but rather an increased reliance on glucose oxidation in the SHR heart.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, UK.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Dodd
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ball
authors.forename: Marie A
authors.initials: MA
authors.lastname: Schroeder
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Le Page
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Atherton
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Heather
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Seymour
authors.forename: Houman
authors.initials: H
authors.lastname: Ashrafian
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology; D002952:Citric Acid Cycle; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D001639:Bicarbonates; D011768:Pyruvate Dehydrogenase Complex; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate