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Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart

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Abstract

Hyperpolarized 13C magnetic resonance is a powerful tool for the study of cardiac metabolism. In this work, we have implemented protocols for the real-time hyperpolarized 13C investigation of Langendorff-perfused rat hearts using both non-selective non-localized spectroscopy and fast spectroscopic imaging. Following [1-13C] pyruvate infusion, we observed both catabolic and anaplerotic metabolic processes resulting in a number of metabolites, including bicarbonate, carbon dioxide, lactate, alanine and aspartate. Employing fast spectroscopic imaging, we were able to observe regional variations in pyruvate perfusion as well as in lactate and bicarbonate production.

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References

  1. F.J. Sutherland, D.J. Hearse, Pharmacol. Res. 41, 613–627 (2000)

    Article  Google Scholar 

  2. T.A. McKinsey, D.A. Kass, Nat. Rev. Drug Discover. 6, 617–635 (2007)

    Article  Google Scholar 

  3. M. Mayr, U. Mayr, Y.L. Chung, X.K. Yin, J.R. Griffiths, O.B. Xul, Proteomics 4, 3751–3761 (2004)

    Article  Google Scholar 

  4. D.J. Hausenloy, A. Tsang, D.M. Yellon, Trends Cardiovasc. Med. 15, 69–75 (2005)

    Article  Google Scholar 

  5. J.M. Salhany, G.M. Pieper, S. Wu, G.L. Todd, F.C. Clayton, R.S. Eliot, J. Mol. Cell. Cardiol. 11, 601–610 (1979)

    Article  Google Scholar 

  6. P.B. Garlick, G.K. Radda, P.J. Seeley, Biochem. Biophys. Res. Commun. 74, 1256–1262 (1977)

    Article  Google Scholar 

  7. R. Southworth, P.B. Garlick, Am. J. Physiol. Heart Circ. Physiol. 285, H316–H324 (2003)

    Google Scholar 

  8. J.F. Unitt, J. Schrader, F. Brunotte, G.K. Radda, A.M. Seymour, Biochim. Biophys. Acta 1133, 115–120 (1992)

    Article  Google Scholar 

  9. L.C. Stewart, J.K. Saunders, R. Deslauriers, D. Bourgeois, J.F.J. Nedelec, Magn. Reson. Med. 30, 655–660 (1993)

    Article  Google Scholar 

  10. D.E. Hoekenga, J.R. Brainard, J.Y. Hutson, Circ. Res. 62, 1065–1074 (1988)

    Article  Google Scholar 

  11. C.J. Hardy, R.G. Weiss, P.A. Bottomley, G. Gerstenblith, Am. Heart J. 122, 795–801 (1991)

    Article  Google Scholar 

  12. M. Beer, T. Seyfarth, J. Sandstede, W. Landschutz, C. Lipke, H. Kostler, M. von Kienlin, K. Harre, D. Hahn, S. Neubauer, J. Am. Coll. Cardiol. 40, 1267–1274 (2002)

    Article  Google Scholar 

  13. P.A. Bottomley, R.G. Weiss, Lancet 351, 714–718 (1998)

    Article  Google Scholar 

  14. M. Scheuermann-Freestone, P.L. Madsen, D. Manners, A.M. Blamire, R.E. Buckingham, P. Styles, G.K. Radda, S. Neubauer, K. Clarke, Circulation 107, 3040–3046 (2003)

    Article  Google Scholar 

  15. J.M. McGavock, I. Lingvay, I. Zib, T. Tillery, N. Salas, R. Unger, B.D. Levine, P. Raskin, R.G. Victor, L.S. Szczepaniak, Circulation 116, 1170–1175 (2007)

    Article  Google Scholar 

  16. J.H. Ardenkjaer-Larsen, B. Fridlund, A. Gram, G. Hansson, L. Hansson, M.H. Lerche, R. Servin, M. Thaning, K. Golman, Proc. Natl. Acad. Sci. USA. 100, 10158–10163 (2003)

    Article  ADS  Google Scholar 

  17. M.E. Merritt, C. Harrison, C. Storey, F.M. Jeffrey, A.D. Sherry, C.R. Malloy, Proc. Natl. Acad. Sci. USA. 104, 19773–19777 (2007)

    Article  ADS  Google Scholar 

  18. M.E. Merritt, C. Harrison, C. Storey, A.D. Sherry, C.R. Malloy, Magn. Reson. Med. 60, 1029–1036 (2008)

    Article  Google Scholar 

  19. M.A. Schroeder, L.E. Cochlin, L.C. Heather, K. Clarke, G.K. Radda, D.J. Tyler, Proc. Natl. Acad. Sci. USA. 105, 12051–12056 (2008)

    Article  ADS  Google Scholar 

  20. H.J. Atherton, M.S. Dodd, L.C. Heather, M.A. Schroeder, J.L. Griffin, G.K. Radda, K. Clarke, D.J. Tyler, Circulation 123, U2134–U2552 (2011)

    Article  Google Scholar 

  21. M.A. Schroeder, H.J. Atherton, D.R. Ball, M.A. Cole, L.C. Heather, J.L. Griffin, K. Clarke, G.K. Radda, D.J. Tyler, FASEB J. 23, 2529–2538 (2009)

    Article  Google Scholar 

  22. A.P. Chen, R.E. Hurd, M.A. Schroeder, A.Z. Lau, Y.-p. Gu, W.W. Lam, J. Barry, J. Tropp, C.H. Cunningham, NMR Biomed. 25, 305–311 (2012)

    Google Scholar 

  23. P.R. Jensen, T. Peitersen, M. Karlsson, R. in't Zandt, A. Gisselsson, G. Hansson, S. Meier, M.H. Lerche, J. Biol. Chem. 284, 36077–36082 (2009)

    Google Scholar 

  24. K. Golman, J.S. Petersson, P. Magnusson, E. Johansson, P. Akeson, C.M. Chai, G. Hansson, S. Mansson, Magn. Reson. Med. 59, 1005–1013 (2008)

    Article  Google Scholar 

  25. R. Southworth, J.L. Dearling, R.A. Medina, A.A. Flynn, R.B. Pedley, P.B. Garlick, Eur. J. Nucl. Med. Mol. Imaging 29, 1334–1341 (2002)

    Article  Google Scholar 

  26. A.E. Arai, J. Cardiovasc. Pharmacol. Ther. 16, 313–320 (2011)

    Article  Google Scholar 

  27. C.H. Cunningham, A.P. Chen, M.J. Albers, J. Kurhanewicz, R.E. Hurd, Y.F. Yen, J.M. Pauly, S.J. Nelson, D.B. Vigneron, J. Magn. Reson. 187, 357–362 (2007)

    Article  ADS  Google Scholar 

  28. C.H. Cunningham, A.P. Chen, M. Lustig, B.A. Hargreaves, J. Lupo, D. Xu, J. Kurhanewicz, R.E. Hurd, J.M. Pauly, S.J. Nelson, D.B. Vigneron, J. Magn. Reson. 193, 139–146 (2008)

    Article  ADS  Google Scholar 

  29. A.Z. Lau, A.P. Chen, N.R. Ghugre, V. Ramanan, W.W. Lam, K.A. Connelly, G.A. Wright, C.H. Cunningham, Magn. Reson. Med. 64, 1323–1331 (2010)

    Article  Google Scholar 

  30. P. Mansfield, Magn. Reson. Med. 1, 370–386 (1984)

    Article  Google Scholar 

  31. M. Skrzypiec-Spring, B. Grotthus, A. Szelag, R. Schulz, J. Pharmacol. Toxicol. Methods 55, 113–126 (2007)

    Article  Google Scholar 

  32. R.M. Bell, M.M. Mocanu, D.M. Yellon, J. Mol. Cell. Cardiol. 50, 940–950 (2011)

    Article  Google Scholar 

  33. E. Heijman, W. de Graaf, P. Niessen, A. Nauerth, G. van Eys, L. de Graaf, K. Nicolay, G.J. Strijkers, NMR Biomed. 20, 439–447 (2007)

    Article  Google Scholar 

  34. L. Vanhamme, A. van den Boogaart, S. Van Huffel, J. Magn. Reson. 129, 35–43 (1997)

    Article  ADS  Google Scholar 

  35. A. Naressi, C. Couturier, J.M. Devos, M. Janssen, C. Mangeat, R. de Beer, D. Graveron-Demilly, MAGMA 12, 141–152 (2001)

    Article  Google Scholar 

  36. M.A. Schroeder, P. Swietach, H.J. Atherton, F.A. Gallagher, P. Lee, G.K. Radda, K. Clarke, D.J. Tyler, Cardiovasc. Res. 86, 82–91 (2010)

    Article  Google Scholar 

  37. M.E. Merritt, C. Harrison, A.D. Sherry, C.R. Malloy, S.C. Burgess, Proc. Natl. Acad. Sci. USA. 108, 19084–19089 (2011)

    Article  ADS  Google Scholar 

  38. K.X. Moreno, S.M. Sabelhaus, M.E. Merritt, A.D. Sherry, C.R. Malloy, Am. J. Physiol. Heart Circul. Physiol. 298, H1556–H1563 (2010)

    Article  Google Scholar 

  39. C.R. Malloy, A.D. Sherry, F.M.H. Jeffrey, J. Biol. Chem. 263, 6964–6971 (1988)

    Google Scholar 

  40. J.C. Chatham, B. Bouchard, C. Des Rosiers, Mol. Cell. Biochem. 249, 105–112 (2003)

    Article  Google Scholar 

  41. R. Southworth, K.A.B. Davey, A. Warley, P.B. Garlick, Am. J. Physiol. Heart Circul. Physiol. 292, H378–H386 (2007)

    Article  Google Scholar 

  42. P.E. Larson, A.B. Kerr, A.P. Chen, M.S. Lustig, M.L. Zierhut, S. Hu, C.H. Cunningham, J.M. Pauly, J. Kurhanewicz, D.B. Vigneron, J. Magn. Reson. 194, 121–127 (2008)

    Article  ADS  Google Scholar 

  43. H. Pedersen, S. Kozerke, S. Ringgaard, K. Nehrke, W.Y. Kim, Magn. Reson. Med. 62, 706–716 (2009)

    Article  Google Scholar 

Download references

Acknowledgments

We are grateful to support provided by The Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC under Grant number WT 088641/Z/09/Z, an Engineering and Physical Science Research Council studentship, the British Heart Foundation project Grant PG/10/020, a Royal Society research grant and the Swiss National Science Foundation, Grant #CR3213_132671/1. We thank Craig Cummings for construction of the home-built 13C coil and Dr. Steven Reynold for the loan of the dual tuned 1H/13C birdcage coil.

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Authors and Affiliations

  1. Division of Imaging Sciences and Biomedical Engineering, King’s College London, St Thomas Hospital, London, UK

    Erika Mariotti, Joel T. Dunn, Rodolfo A. Medina, Richard Southworth, Sebastian Kozerke & Thomas R. Eykyn

  2. Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092, Zurich, Switzerland

    Kilian Weiss & Sebastian Kozerke

  3. CRUK and EPSRC Cancer Imaging Centre, Royal Marsden NHS Trust, The Institute of Cancer Research, Sutton, UK

    Deborah K. Hill, Matthew R. Orton & Thomas R. Eykyn

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  1. Kilian Weiss
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Correspondence to Sebastian Kozerke or Thomas R. Eykyn.

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K. Weiss and E. Mariotti contributed equally to this work.

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Weiss, K., Mariotti, E., Hill, D.K. et al. Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart. Appl Magn Reson 43, 275–288 (2012). https://doi.org/10.1007/s00723-012-0349-2

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  • DOI: https://doi.org/10.1007/s00723-012-0349-2

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