The Present and Future
State-of-the-Art Review
The Pathophysiological Role of Interstitial Sodium in Heart Failure

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Abstract

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.

Key Words

endothelial dysfunction
endothelial glycocalyx
glycosaminoglycan
interstitium
proteoglycan

Abbreviations and Acronyms

ADHF
acute decompensated heart failure
AVP
arginine vasopressin
eGC
endothelial glycocalyx
EnNaC
endothelial sodium channel
GAG
glycosaminoglycan
HF
heart failure
Na+
sodium
NO
nitric oxide
TBW
total body water
VEGF-C
vascular endothelial growth factor C

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Drs. Nijst, Verbrugge, Grieten, and Mullens are researchers for the Limburg Clinical Research Program (LCRP), UHasselt-ZOL-Jessa, which is supported by the Foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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