Excess sodium is deleterious on endothelial and glycocalyx barrier function: A microfluidic study.

Background: Hypernatremia is a common problem affecting critically ill patients, whether due to underlying pathology or the subsequent result of hypertonic fluid resuscitation. Numerous studies have been published, suggesting that hypernatremia may adversely affect the vascular endothelial glycocalyx. Our study aimed to evaluate if high sodium concentration would impair the endothelial and glycocalyx barrier function and if stress conditions that simulate the shock microenvironment would exacerbate any observed adverse effects of hypernatremia.

Methods: Human umbilical vein endothelial cells (HUVEC) were cultured in microfluidic channels subjected to flow conditions overnight to stimulate glycocalyx growth. Cells were then subjected to sodium (Na) concentrations of either 150 mEq/L or 160 mEq/L, with Hepes solution applied to media to maintain physiologic pH. Subsets of HUVEC were also exposed to hypoxia/reoxygenation and epinephrine (HR + Epi) to simulate shock insult, then followed by Na treatment. Perfusate was then collected 60 minutes and 120 minutes following treatments. Relevant biomarkers were then evaluated and HUVEC underwent fluorescent staining followed by microscopy.

Results: Glycocalyx degradation as indexed by hyaluronic acid and syndecan-1 was elevated in all subgroups, particularly those subjected to HR + Epi with Na 160 mEq/L. Thickness of the glycocalyx as evaluated by fluorescent microscopy was reduced to half of baseline with Na 160 mEq/L and to one third of baseline with additional insult of HR + Epi. Endothelial activation/injury as indexed by soluble thrombomodulin was elevated in all subgroups. A profibrinolytic coagulopathy phenotype was demonstrated in all subgroups with increased tissue plasminogen activator levels and decreased plasminogen activator inhibitor-1 levels.

Conclusion: Our data suggest that hypernatremia results in degradation of the endothelial glycocalyx with further exacerbation by shock conditions. A clinical study using clinical measurements of the endothelial glycocalyx in critically ill or injured patients with acquired hypernatremia would be warranted.