Time-Dependent Dynamics Required for the Degradation and Restoration of the Vascular Endothelial Glycocalyx Layer in Lipopolysaccharide-Treated Septic Mice

Abstract

The endothelial glycocalyx (GCX) plays a key role in the development of organ failure following sepsis. Researchers have investigated GCX degradation caused by pathological conditions. Nonetheless, the GCX restoration process remains poorly understood. Herein, we developed a model in which GCX restoration could be reproduced in mice using in vivo imaging and a dorsal skinfold chamber (DSC). The severity of sepsis was controlled by adjusting the dose of lipopolysaccharide (LPS) used to trigger GCX degradation in BALB/c mice. We evaluated the GCX thickness, leukocyte-endothelial interactions, and vascular permeability using in vivo imaging through DSC under intravital microscopy. The plasma concentration of syndecan-1(Sdc-1), a GCX structural component, was also determined as a marker of GCX degradation. Thus, we developed a reproducible spontaneous GCX recovery model in mice. Degraded GCX was restored within 24 h by the direct visualization of the endothelial GCX thickness, and leukocyte-endothelial interactions. In contrast, indirectly related indicators of recovery from sepsis, such as body weight and blood pressure, required a longer recovery time. This model can be used to study intractable angiopathy following sepsis.

Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study

“…Data show that recovery of the hemodynamically significant glycocalyx layer may take up to several days after various lesions [ 38 ]. However, under specific conditions, endothelial cells appear to have the potential to regenerate the glycocalyx entirely within 24 h from violation [ 38 , 39 ]. One research showed glycocalyx recovery during experimental hemorrhagic shock in rats within 1 h after administration of 15 mL/kg of fresh-frozen plasma [ 40 ].…”

Insights into the Molecular Mechanism of Endothelial Glycocalyx Dysfunction during Heart Surgery

“…Research on animals suggests that the endothelium glycocalyx takes five to seven days to restore after shedding [90]. However, clinical investigations have shown that this process occurs much faster [58,91].…”