In Vivo Assessment of Metabolism in the Hypertensive Rat Heart using Hyperpolarized [1-13C] & [2-13C]pyruvate

Michael Samuel Dodd^1,2, Daniel Ball¹, Marie A. Schroeder¹, Helen J. Atherton¹, Lydia Le Page¹, George K. Radda¹, Houman Ashrafian², Hugh Watkins², Kieran Clarke¹, Damian J. Tyler¹

Spontaneously hypertensive rats (SHRs) display hypertension, insulin resistance and concentric hypertrophy. There is hypothesised to be a switch to a glycolytic phenotype in SHRs. Using hyperpolarized magnetic resonance spectroscopy, via dynamic nuclear polarization, the metabolism of [1-¹³C] and [2-¹³C]pyruvate was observed. This showed a 63% increase in PDH flux in SHRs and an increase in label incorporation into acetylcarnitine and glutmate pools, which is proportional to the increase in PDH flux. No classical switch to a glycolytic phenotype was observed, as flux into lactate remained unchanged between groups. However, an increased reliance on glucose oxidation through PDH, was observed.