Hyperpolarized 13C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart

European Journal of Heart Failure

Volumn 15, Issue 2, 2013, Pages 130-140

  Schroeder, Marie A ^a,b   Lau, Angus Z ^a,c   Chen, Albert P ^d   Gu, Yiping ^a   Nagendran, Jeevan ^e   Barry, Jennifer ^a   Hu, Xudong ^f   Dyck, Jason R B ^e   Tyler, Damian J ^b   Clarke, Kieran ^b   Connelly, Kim A ^a,f   Wright, Graham A ^a,c   Cunningham, Charles H ^a,c  

^a SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF TORONTO   (Canada)

^d GE HEALTHCARE   (Canada)

^e UNIVERSITY OF ALBERTA   (Canada)

^f ST MICHAEL'S HOSPITAL   (Canada)

Author keywords

Magnetic resonance

Indexed keywords

ADENOSINE TRIPHOSPHATE; BICARBONATE; CARNITINE PALMITOYLTRANSFERASE I; CREATINE PHOSPHATE; GLUTAMIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PROTEIN KINASE B; PYRUVATE DEHYDROGENASE COMPLEX; PYRUVATE DEHYDROGENASE KINASE 4; PYRUVIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONGESTIVE CARDIOMYOPATHY; FEMALE; GENE EXPRESSION; HEART FAILURE; HEART LEFT VENTRICLE ENDDIASTOLIC VOLUME; HEART PACING; HYPERPOLARIZATION; IN VIVO STUDY; NONHUMAN; PHOSPHORUS NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ADENOSINE TRIPHOSPHATE; ANIMALS; BICARBONATES; CARBON ISOTOPES; CARDIAC PACING, ARTIFICIAL; CARDIAC VOLUME; CARDIOMYOPATHY, DILATED; CARNITINE O-PALMITOYLTRANSFERASE; CITRIC ACID CYCLE; DISEASE MODELS, ANIMAL; ENERGY METABOLISM; GENE EXPRESSION; GLUTAMIC ACID; GLYCOLYSIS; HEART FAILURE; MAGNETIC RESONANCE IMAGING; MAGNETIC RESONANCE SPECTROSCOPY; MEMBRANE TRANSPORT PROTEINS; PHOSPHOCREATINE; PPAR ALPHA; PROTEIN KINASES; PYRUVATE DEHYDROGENASE COMPLEX; PYRUVIC ACID; SWINE; VENTRICULAR DYSFUNCTION, LEFT;

EID: 84872515091     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfs192     Document Type: Article

References (44)

1. Neubauer S. The failing heart-an engine out of fuel. N Engl J Med 2007;356: 1140-1151. (Pubitemid 46425598)
2. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005;85:1093-1129. (Pubitemid 40894649)
3. Neubauer S, Krahe T, Schindler R, Horn M, Hillenbrand H, Entzeroth C, Mader H, Kromer EP, Riegger GA, Lackner K, Ertl G. 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. Circulation 1992;86: 1810-1818.
4. Shen WQ, Asai K, Uechi M, Mathier MA, Shannon RP, Vatner SF, Ingwall JS. Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs-a compensatory role for the parallel loss of creatine. Circulation 1999;100:2113-2118. (Pubitemid 29532064)
5. Beanlands RS, Nahmias C, Gordon E, Coates G, deKemp R, Firnau G, Fallen E. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: a doubleblind, placebo-controlled, positron-emission tomography study. Circulation 2000; 102:2070-2075.
6. Ukkonen H, Beanlands RS, Burwash IG, de Kemp RA, Nahmias C, Fallen E, Hill MR, Tang AS. Effect of cardiac resynchronization on myocardial efficiency and regional oxidative metabolism. Circulation 2003;107:28-31. (Pubitemid 36070928)
7. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 1996;94: 2837-2842. (Pubitemid 26411749)
8. Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, Taegtmeyer H. Metabolic gene expression in fetal and failing human heart. Circulation 2001;104: 2923-2931. (Pubitemid 33139104)
9. Lei B, Lionetti V, Young ME, Chandler MP, d'Agostino C, Kang E, Altarejos M, Matsuo K, Hintze TH, Stanley WC, Recchia FA. Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. J Mol Cell Cardiol 2004;36:567-576. (Pubitemid 38469947)
10. Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 2004;110: 955-961. (Pubitemid 39128621)
11. Opie LH, Knuuti J. The adrenergic-fatty acid load in heart failure. J Am Coll Cardiol 2009;54:1637-1646.
12. Osorio JC, Stanley WC, Linke A, Castellari M, Diep QN, Panchal AR, Hintze TH, Lopaschuk GD, Recchia FA. Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid×receptor-alpha in pacing-induced heart failure. Circulation 2002;106:606-612. (Pubitemid 34827712)
13. Recchia FA, McConnell PI, Bernstein RD, Vogel TR, Xu X, Hintze TH. Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog. Circ Res 1998;83: 969-979. (Pubitemid 28520926)
14. Taylor M, Wallhaus TR, Degrado TR, Russell DC, Stanko P, Nickles RJ, Stone CK. An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in Patients with Congestive Heart Failure. J Nucl Med 2001;42:55-62. (Pubitemid 32104778)
15. Paolisso G, Gambardella A, Galzerano D, D'Amore A, Rubino P, Verza M, Teasuro P, Varricchio M, D'Onofrio F. Total-body and myocardial substrate oxidation in congestive heart failure. Metabolism 1994;43:174-179. (Pubitemid 24061849)
16. Nikolaidis LA, Sturzu A, Stolarski C, Elahi D, Shen YT, Shannon RP. The development of myocardial insulin resistance in conscious dogs with advanced dilated car-diomyopathy. Cardiovasc Res 2004;61:297-306. (Pubitemid 38091770)
17. Paternostro G, Camici PG, Lammerstma AA, Marinho N, Baliga RR, Kooner JS, Radda GK, Ferrannini E. Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography. J Clin Invest 1996;98:2094-2099. (Pubitemid 26376298)
18. Horowitz JD, Kennedy JA. Time to address the cardiac metabolic 'triple whammy' ischemic heart failure in diabetic patients. J Am Coll Cardiol 2006;48:2232-2234.
19. Budoff MJ, Gupta M. Radiation exposure from cardiac imaging procedures. J Am Coll Cardiol 2010;56:712-714.
20. Ingwall JS, Weiss RG. Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 2004;95:135-145. (Pubitemid 38988679)
21. Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K. Increase in signal-to-noise ratio of.10, 000 times in liquid-state NMR. Proc Natl Acad Sci USA 2003;100:10158-10163. (Pubitemid 37071849)
22. Golman K, Petersson JS, Magnusson P, Johansson E, Akeson P, Chai CM, Hansson G, Mansson S. Cardiac metabolism measured noninvasively by hyperpo-larized 13C MRI. Magn Reson Med 2008;59:1005-1013. (Pubitemid 351590513)
23. Schroeder M, Cochlin L., Heather L., Clarke K., Radda G., Tyler D. In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci USA 2008;105:12051-12056.
24. Merritt ME, Harrison C, Storey C, Jeffrey FM, Sherry AD, Malloy CR. Hyperpo-larized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc Natl Acad Sci USA 2007;104:19773-19777.
25. Schroeder MA, Clarke K, Neubauer S, Tyler DJ. Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment of cardiovascular disease. Circulation 2011;124:1580-1594.
26. Schroeder MA, Atherton HJ, Ball DR, Cole MA, Heather LC, Griffin JL, Clarke K, Radda GK, Tyler DJ. Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J 2009;23: 2529-2538.
27. Lau AZ, Chen AP, Ghugre NR, Ramanan V, Lam WW, Connelly KA, Wright GA, Cunningham CH. Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart. Magn Reson Med 2010;64:1323-1331.
28. Golman K, in't Zandt R., Thaning M. Real-time metabolic imaging. Proc Natl Acad Sci USA 2006;103:11270-11275. (Pubitemid 44156508)
29. Lau A, Chen, Schroeder, Lam, Gu, Barry, Cunningham. Free-breathing cardiac and respiratory-gated imaging of hyperpolarized pyruvate and bicarbonate in the heart. International Society of Magnetic Resonance in Medicine. Montreal, Canada, 2011.
30. Malloy CR, Merritt ME, Sherry AD. Could 13C MRI assist clinical decision-making for patients with heart disease? NMR Biomed 2011;24:973-979.
31. Schroeder MA, Atherton HJ, Dodd MS, Lee P, Cochlin LE, Radda GK, Clarke K, Tyler DJ. The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. Circ Cardiovasc. Imaging 2012;5:201-209.
32. Atherton HJ, Schroeder MA, Dodd MS, Heather LC, Carter EE, Cochlin LE, Nagel S, Sibson NR, Radda GK, Clarke K, Tyler DJ. Validation of the in vivo assessment of pyruvate dehydrogenase activity using hyperpolarised (13) C MRS. NMR. Biomed 2010;24:201-208.
33. Lau AZ, Chen AP, Cunningham CH. Integrated Bloch-Siegert B(1) mapping and multislice imaging of hyperpolarized (1) (3)C pyruvate and bicarbonate in the heart. Magn Reson Med 2012;67:62-71.
34. Di Lisa F, Fan CZ, Gambassi G, Hogue BA, Kudryashova I, Hansford RG. Altered pyruvate dehydrogenase control and mitochondrial free Ca2+ in hearts of cardiomyopathic hamsters. Am J Physiol 1993;264:H2188-H2197. (Pubitemid 23205993)
35. Atherton HJ, Dodd MS, Heather LC, Schroeder MA, Griffin JL, Radda GK, Clarke K, Tyler DJ. Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study. Circulation 2011;123:2552-2561.
36. Pound KM, Sorokina N, Ballal K, Berkich DA, Fasano M, Lanoue KF, Taegtmeyer H, O'DonnellJM, Lewandowski ED. Substrate-enzyme competition attenuates upregulated anaplerotic flux through malic enzyme in hypertrophied rat heart and restores triacylglyceride content: attenuating upregulated anaplero-sis in hypertrophy. Circ Res 2009;104:805-812.
37. Sorokina N, O'Donnell JM, McKinney RD, Pound KM, Woldegiorgis G, LaNoue KF, Ballal K, Taegtmeyer H, Buttrick PM, Lewandowski ED. Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmi-toyltransferase I activity characterizes inefficiency in energy metabolism in hypertrophied hearts. Circulation 2007;115:2033-2041. (Pubitemid 46625954)
38. Caruso M, Maitan MA, Bifulco G, Miele C, Vigliotta G, Oriente F, Formisano P, Beguinot F. Activation and mitochondrial translocation of protein kinase Cdelta are necessary for insulin stimulation of pyruvate dehydrogenase complex activity in muscle and liver cells. J Biol Chem 2001;276:45088-45097.
39. Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 2005;112:3280-3288. (Pubitemid 43739373)
40. Halestrap AP, Price NT. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 1999;343:281-299. (Pubitemid 29511759)
41. Johannsson E, Lunde PK, Heddle C, Sjaastad I, Thomas MJ, Bergersen L, Halestrap AP, Blackstad TW, Ottersen OP, Sejersted OM. Upregulation of the cardiac monocarboxylate transporter MCT1 in a rat model of congestive heart failure. Circulation 2001;104:729-734. (Pubitemid 32738531)
42. Chen AP, Hurd RE, Schroeder MA, Lau AZ, Gu YP, Lam WW, Barry J, Tropp J, Cunningham CH. Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1, 2- (13)C2]pyruvate in vivo. NMR Biomed 2012;25:305-311.
43. Ardehali H, Sabbah HN, Burke MA, Sarma S, Liu PP, Cleland JG, Maggioni A, Fonarow GC, Abel ED, Campia U, Gheorghiade M. Targeting myocardial sub-strate metabolism in heart failure: potential for new therapies. Eur J Heart Fail 2012;14:120-129.
44. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86:580-588. (Pubitemid 30165050)