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dc.contributor.authorMariotti, E
dc.contributor.authorOrton, MR
dc.contributor.authorEerbeek, O
dc.contributor.authorAshruf, JF
dc.contributor.authorZuurbier, CJ
dc.contributor.authorSouthworth, R
dc.contributor.authorEykyn, TR
dc.date.accessioned2018-07-25T14:40:55Z
dc.date.issued2016-04
dc.identifier4
dc.identifier.citationNMR IN BIOMEDICINE, 2016, 29 pp. 377 - 386
dc.identifier.issn0952-3480
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2147
dc.identifier.eissn1099-1492
dc.identifier.doi10.1002/nbm.3464
dc.description.abstractHyperpolarized C-13 MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-C-13] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-C-13] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect. (c) 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
dc.format.extent377 - 386
dc.languageeng
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleModeling non-linear kinetics of hyperpolarized [1-C-13] pyruvate in the crystalloid-perfused rat heart
dc.typeJournal Article
rioxxterms.versionofrecord10.1002/nbm.3464
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNMR IN BIOMEDICINE
pubs.notesaffiliation: Eykyn, TR (Reprint Author), St Thomas Hosp, Kings Coll London, Div Imaging Sci & Biomed Engn, London SE1 7EH, England. Mariotti, E.; Southworth, R.; Eykyn, T. R., St Thomas Hosp, Kings Coll London, Kings Hlth Partners, Dept Imaging Chem & Biol,Div Imaging Sci & Biomed, London SE1 7EH, England. Orton, M. R.; Eykyn, T. R., Inst Canc Res, CR UK & EPSRC Canc Imaging Ctr, Div Radiotherapy & Imaging, Sutton SM2 5NG, Surrey, England. Orton, M. R.; Eykyn, T. R., Royal Marsden NHS Trust, Sutton SM2 5NG, Surrey, England. Eerbeek, O., UvA, AMC, Dept Anat Embryol & Physiol, Amsterdam, Netherlands. Ashruf, J. F.; Zuurbier, C. J., UvA, AMC, Dept Anesthesiol, LEICA, Amsterdam, Netherlands. Southworth, R.; Eykyn, T. R., St Thomas Hosp, Kings Coll London, British Heart Fdn Ctr Res Excellence, Rayne Inst, London SE1 7EH, England. keywords: hyperpolarized C-13; dynamic nuclear polarization (DNP); cardiac metabolism; Langendorff perfused heart keywords-plus: MAGNETIC-RESONANCE-SPECTROSCOPY; IN-VIVO ASSESSMENT; LACTATE DEHYDROGENASE; MYOCARDIAL UPTAKE; C-13; FLUX; METABOLISM; GLUCOSE; CELLS; NMR research-areas: Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy web-of-science-categories: Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy author-email: [email protected] researcherid-numbers: Southworth, Richard/B-7855-2009 Eykyn, Thomas/J-3284-2016 orcid-numbers: Southworth, Richard/0000-0002-7904-8335 Eykyn, Thomas/0000-0003-1768-3808 funding-acknowledgement: National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London; British Heart Foundation [RE/08/003, PG/10/20/28211]; Centre of Excellence in Medical Engineering - Wellcome Trust; EPSRC [WT 088641/Z/09/Z]; EPSRC PhD studentship; King’s College London; UCL Comprehensive Cancer Imaging Centre - CRUK; MRC; Department of Health (DoH) (England); CRUK; EPSRC Cancer Imaging Centre; DoH (England) [C1060/A10334]; British Heart Foundation [PG/10/20/28211] funding-text: The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London; the British Heart Foundation award (RE/08/003) and project grant PG/10/20/28211; the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC under grant number WT 088641/Z/09/Z; an EPSRC PhD studentship and the King’s College London and UCL Comprehensive Cancer Imaging Centre funded by the CRUK and EPSRC in association with the MRC and Department of Health (DoH) (England). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the DoH. TRE and MRO are grateful for support from the CRUK and EPSRC Cancer Imaging Centre in association with the MRC and the DoH (England) grant C1060/A10334. number-of-cited-references: 36 times-cited: 2 usage-count-last-180-days: 0 usage-count-since-2013: 2 journal-iso: NMR Biomed. doc-delivery-number: DI3HD unique-id: ISI:000373388800002 oa: gold_or_bronze da: 2018-07-25
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.volume29
pubs.embargo.termsNot known
pubs.oa-locationhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/nbm.3464
icr.researchteamMagnetic Resonanceen_US
dc.contributor.icrauthorOrton, Matthewen


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