You are here

Article Text

Article menu

Download PDFPDF

Abstracts
P1 Causal link between intracellular sodium overload and metabolic remodelling in the heart: uncoupling ATP supply and demand?
Free
  1. D Aksentijević1,
  2. A Karlstädt2,
  3. M Basalay1,
  4. BA O’Brien1,
  5. A Thakker3,
  6. D Tennant3,
  7. W Fuller4,
  8. H Taegtmayer2,
  9. TR Eykyn5,
  10. MJ Shattock1
  1. 1British Heart Foundation Centre of Research Excellence, King’s College London, The Rayne Institute, St Thomas’ Hospital, London, UK
  2. 2Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Centre at Houston, McGovern Medical School, Houston, Texas, USA
  3. 3Institute of Metabolism and Systems Research, College of Medical and Dental Sciences University of Birmingham, Edgbaston, Birmingham, UK
  4. 4Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  5. 5Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, King’s College London, St Thomas’ Hospital, London, UK

Abstract

Rationale Intracellular Na elevation is a hallmark of the ischaemic and failing heart – pathologies in which both acute and chronic metabolic remodelling occur.

Objective To assess whether acute (75 µM ouabain 100 nM blebbistatin) and chronic myocardial Nai load (PLM3SA mouse) are causally linked to metabolic remodelling and if the failing heart shares a common Na-mediated metabolic ‘fingerprint’.

Methods 23Na, 31P and 13C NMRS were performed in normal and hypertrophied (pressure overload) Langendorff perfused mouse hearts followed by 1 hour NMRS metabolomic profiling, mass spec and in silico modelling.

Results Na overload (acute, chronic (PLM3SA), and hypertrophy 2, 1.3 and 1.4-fold respectively) resulted in common metabolic perturbations: substrate switch (palmitate 35% reduction, glucose 58% increase), flux (TCA cycle, OXPHOS, glycolysis) and metabolomic profile (TCA cycle, glycolysis, anaplerosis) without energetic impairment (PCr/ATP 1.5±0.1 vs control 1.3±0.1). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 during both acute and chronic Na load ameliorated the metabolic changes.

Conclusion Elevated Na leads to complex metabolic alterations preceding any energetic and functional impairment. Early prevention of Na overload and inhibition of Na/Camito could ameliorate metabolic dysregulation in hypertrophy and failure.

http://dx.doi.org/10.1136/heartjnl-2018-BSCR.6

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.