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Myocardial energetics and redox in health and disease
015 Investigating metabolic flux in the hyperthyroid heart using hyperpolarised magnetic resonance
  1. M Dodd
  1. Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

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An increase in circulating thyroid hormone (TH) causes hypertrophy, which is accompanied by an increase in contractility and cardiac output. However, the mechanisms behind these observations are yet to be fully elucidated. TH is an important regulator of energy metabolism and has been shown to control the expression of many important lipolytic and glycolytic enzymes. One such enzyme is pyruvate dehydrogenase kinase, which, via phosphorylation, reduces the activity of pyruvate dehydrogenase (PDH) and thus decreases the conversion of pyruvate to acetyl CoA, a key substrate in ATP synthesis. However, it is not known whether PDH activity is inhibited in the hyperthyroid rat heart. Hyperpolarised substrates increase the sensitivity of magnetic resonance spectroscopy (MRS) so that it is possible to investigate the flux of metabolites through specific enzymes in vivo. In this study, hyperpolarised pyruvate has been used in conjunction with MRS localised to the heart to monitor real time metabolic flux through PDH in hearts of control rats and rats injected with TH (triiodothyronine; T3) for 7 days (n=8 per group). PDH activity measurements were made at baseline and after 7 days of injections. Hyperpolarised pyruvate was injected over 10 s into the anaesthetised rat via the tail vein. The conversion of pyruvate to alanine, lactate and bicarbonate was monitored every 1 s for 1 minute. The bicarbonate/pyruvate ratio was used as a measure of flux through PDH. After 7 days administration of T3, flux through cardiac PDH was reduced by 76% (p<0.01). Thus, hyperpolarised pyruvate has revealed PDH inhibition to contribute to the pathology of the hyperthyroid heart.