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Abstract #3013

In Vivo Hyperpolarized MRI Reveals Metabolic Changes Following Treatment with Mildronate in the Control and Diabetic Heart.

Dragana Savic1, Lorenz Holzner1, Vicky Ball1, M. Kate Curtis1, Lisa C. Heather1, and Damian J. Tyler1

1University of Oxford, Oxford, United Kingdom

L-carnitine acts as a buffer of acetyl-CoA units in the mitochondria, as well as facilitating transport of fatty acids. Mildronate can block the biosynthesis of L-carnitine and its uptake by inhibiting CPT-1. The purpose of this study was to investigate the effect of Mildronate treatment on cardiac function and metabolism in the healthy and the diabetic rat heart. We show that daily injections of Mildronate can alter cardiac metabolism in the in-vivo diabetic and healthy rat heart, without any functional changes, and surprisingly Mildronate can increase flux through pyruvate dehydrogenase. Such studies will allow a better understanding of the interactions between metabolism and function in the diabetic heart and may provide new insight into novel therapeutics.

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