The pathophysiologic role of interstitial sodium in heart failure

Abstract

The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Naþ) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Naþ 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 Naþ 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 Naþ and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hence, a better appreciation of this new Naþ “compartment” might improve current management of HF. (J Am Coll Cardiol 2015;65:378–88) © 2015 by the American College of Cardiology Foundation.