Damian John Tyler1, Marie Allen Schroeder1, Helen Jennifer Atherton1, Daniel R. Ball1, Mark Aaron Cole1, Lisa Claire Heather1, Julian L. Griffin2, Kieran Clarke1, George K. Radda1
1Physiology, Anatomy & Genetics, University of Oxford, Oxford, Oxfordshire, UK; 2Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, UK
The Krebs cycle plays a fundamental role in cardiac energy production and is often implicated in energetic imbalances characteristic of heart disease. This study presents a novel magnetic resonance spectroscopy technique that enables real-time monitoring of Krebs cycle metabolism in whole hearts. Hyperpolarized [2-13C]pyruvate was infused into isolated perfused hearts, in both healthy and ischaemic states. The conversion of pyruvate to lactate, acetyl-carnitine, citrate and glutamate was observed. Following ischaemia, the appearance of 13C-labelled citrate and glutamate was decreased relative to the healthy state, indicating that hyperpolarized [2-13C]pyruvate may be useful when studying impaired Krebs cycle metabolism in heart disease.
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