Hyperpolarized 13C magnetic resonance reveals early‐ and late‐onset changes to in vivo pyruvate metabolism in the failing heart. (February 2013)

• Record Type: Journal Article
• Authors: Schroeder, Marie A.; Lau, Angus Z.; Chen, Albert P.; Gu, Yiping; Nagendran, Jeevan; Barry, Jennifer; Hu, Xudong; Dyck, Jason R.B.; Tyler, Damian J.; Clarke, Kieran; Connelly, Kim A.; Wright, Graham A.; Cunningham, Charles H.
• Is Part Of: European journal of heart failure. Volume 15:Number 2(2013)
• Page Start: 130
• Page End: 140
• Publication Date: 2013-02
• Subjects: Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1093/eurjhf/hfs192
• Languages: English
• ISSNs: 1388-9842

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ejhfhfs192-sec-0001" sec-type="section"> <title>Aims</title> <p>Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized <sup>13</sup>C magnetic resonance (MR), in which <sup>13</sup>C‐labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non‐invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non‐invasive hyperpolarized [<sup>13</sup>C]pyruvate with MR, the profile of <italic>in vivo</italic> pyruvate oxidation would change throughout the course of the disease.</p> </sec> <sec id="ejhfhfs192-sec-0002" sec-type="section"> <title>Methods and results</title> <p>Dilated cardiomyopathy (DCM) was induced in pigs (<italic>n</italic> = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine‐MRI assessed cardiac structure and function; hyperpolarized [2‐<sup>13</sup>C]pyruvate was administered intravenously, and <sup>13</sup>C MRS monitored [<sup>13</sup>C]glutamate production; <sup>31</sup>P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1‐<sup>13</sup>C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)‐mediated pyruvate oxidation via [<sup>13</sup>C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [<sup>13</sup>C]glutamate production decreased by 51%. After clinical features of DCM appeared, end‐diastolic volume increased by 40% and [<sup>13</sup>C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two‐fold, and phosphorylated <italic>Akt</italic> decreased by half. Peroxisome proliferator‐activated receptor‐α and carnitine palmitoyltransferase‐1 gene expression decreased by a half and a third, respectively.</p> </sec> <sec id="ejhfhfs192-sec-0003" sec-type="section"> <title>Conclusion</title> <p>Despite early changes associated with cardiac energetics and <sup>13</sup>C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized <sup>13</sup>C MR may be important to characterize metabolic changes that occur during heart failure progression.</p> </sec> </abstract>