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Abstract #3521

Investigating the Role of PDH Inhibition on the Development of Hypertrophy in the Hyperthyroid Rat Heart

Helen J. Atherton1,2, Michael S. Dodd1, Lisa C. Heather1, Marie A. Schroeder1, Julian L. Griffin2, George K. Radda1, Kieran Clarke1, Damian J. Tyler1

1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; 2Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

Hyperthyroidism, caused by an elevated level of thyroid hormones, leads to an increase in heart rate, contractility and cardiac output. Cardiac hypertrophy is another effect of hyperthyroidism and, although the hypertrophy is initially beneficial, it can lead to heart failure. The aim of this work was to determine whether alleviating the known inhibition of pyruvate dehydrogenase (PDH) in the hyperthyroid heart using dichloroacetate (DCA) would affect the response to hyperthyroidism. Using hyperpolarized MRS and CINE MRI, we found that DCA treatment increased PDH flux by 134% and significantly reduced the level of hypertrophy observed in the hyperthyroid rat heart.