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Abstract #0786

Mitochondrial dysfunction in a rat model of doxorubicin-induced heart failure assessed by hyperpolarized 13C MRS

Kerstin N Timm1, Charith Perera1, Vicky Ball1, John A Henry1, Matthew Kerr1, Michael S Dodd1, Jack J Miller1,2,3, James West4, Angela Logan5, Julian L Griffin4, Michael P Murphy5, Lisa C Heather1, and Damian J Tyler1,2

1Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 2Oxford Centre for Magnetic Resonance, John Radcliffe Hospital, Oxford, United Kingdom, 3Department of Physics, University of Oxford, Oxford, United Kingdom, 4Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom, 5MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom

Doxorubicin-chemotherapy can lead to serious cardiac side effects in cancer-patients, culminating in heart failure. Cardiac oxidative stress and impaired energetics are hypothesized to be at the core of this toxicity. We established a clinically relevant rat model of doxorubicin-induced heart failure characterized with CINE MRI by decreased cardiac function. We show here that these functional changes are preceded by a shift from oxidative to anaerobic glucose metabolism measured with hyperpolarized MRS. These changes are likely due to a loss and impairment of mitochondria, which cannot be alleviated with the mitochondrially targeted antioxidant, MitoQ.

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