The pathophysiological role of interstitial sodium in heart failure

Petra Nijst, Frederik H Verbrugge, Lars Grieten, Matthias Dupont, Paul Steels, W H Wilson Tang, Wilfried Mullens

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)


The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Na(+)) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Na(+) is not distributed in the body solely as a free cation, but that it is also bound to large interstitial glycosaminoglycan (GAG) networks in different tissues, which have an important regulatory function. In HF, high Na(+) intake and neurohumoral alterations disrupt GAG structure, leading to loss of the interstitial buffer capacity and disproportionate interstitial fluid accumulation. Moreover, a diminished endothelial GAG network (the endothelial glycocalyx) results in increased vascular resistance and disturbed endothelial nitric oxide production. New imaging modalities can help evaluate interstitial Na(+) and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hence, a better appreciation of this new Na(+) "compartment" might improve current management of HF.

Original languageEnglish
Pages (from-to)378-388
Number of pages11
JournalJournal of the American College of Cardiology
Issue number4
Publication statusPublished - 3 Feb 2015

Bibliographical note

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


  • Animals
  • Endothelium, Vascular/physiology
  • Extracellular Fluid/metabolism
  • Glycosaminoglycans/metabolism
  • Heart Failure/metabolism
  • Humans
  • Sodium/metabolism
  • Water-Electrolyte Balance


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