In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart

Michael S. Dodd, Daniel R. Ball, Marie A. Schroeder, Lydia M. Le Page, Helen J. Atherton, Lisa C. Heather, Anne-Marie Seymour, Houman Ashrafian, Hugh Watkins, Kieran Clarke, Damian J. Tyler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this work was to use hyperpolarized carbon-13 (C-13) 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 -oxidation, and it has previously been shown that in response to hypertrophy the SHR heart switches to a glycolytic/glucose-oxidative phenotype.

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-C-13] and [2-C-13]pyruvate, an 85 increase in C-13 label flux through pyruvate dehydrogenase (PDH) was seen in the SHR heart and C-13 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.

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, C-13 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.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalCardiovascular Research
Volume95
Issue number1
DOIs
Publication statusPublished - 1 Jul 2012

Keywords

  • Dynamic nuclear polarization
  • Spontaneously hypertensive rat
  • Pyruvate dehydrogenase
  • Carbon-13 Magnetic resonance spectroscopy
  • Metabolism
  • MAGNETIC-RESONANCE-SPECTROSCOPY
  • PYRUVATE-DEHYDROGENASE KINASE
  • DEFECTIVE FATTY-ACID
  • INSULIN-RESISTANCE
  • GLUCOSE-METABOLISM
  • ENERGY-METABOLISM
  • ALTERED GLUCOSE
  • BLOOD-PRESSURE
  • C-13
  • HYPERTROPHY

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