The protective effect of hydroxyethyl starch solution on the glycocalyx layer in an acute hemorrhage mouse model

Abstract

Purpose Fluid therapy focused on glycocalyx (GCX) protection in hemorrhagic shock is a current focus of research. Hydroxyethyl starch (HES) solution is commonly used for fluid resuscitation; however, its effects on the GCX remain unclear. The primary aim of this study was to explore the protective effect of HES130 in maintaining GCX thickness and reducing plasma syndecan-1 expression. Methods An acute hemorrhage murine model with the dorsal skin chambers was used to measure GCX thickness and to evaluate vascular permeability. Groups of mice were treated with normal saline (NS), albumin (NS-A), HES130 (NS-V), or no exsanguination or infusion (C). We measured syndecan-1 plasma concentrations, performed blood gas analysis, and analyzed the 7-day cumulative mortality. Results GCX thickness in NS mice was significantly reduced compared to that in group C, but no other groups showed a difference compared to group C. The plasma concentration of syndecan-1 was significantly higher in NS mice than in group C. There were no significant differences in the fluorescence intensity of dextran in the interstitial space. HES70 leakage was suppressed in NS-V mice compared to those in other groups. HES70 was localized to the inner vessel wall in C, NS, and NS-A mice, but not in group NS-V. Blood gas analysis indicated that pH and lactate showed the greatest improvements in NS-V mice. The 7-day cumulative mortality rate was the highest in group NS. Conclusion Resuscitation with HES130 protected the GCX and suppressed vascular permeability of HES70 during early stages of acute massive hemorrhage.

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

“…Along with the unveiling of the GCX, adhesion molecules are exposed and facilitate ligand–receptor interactions that promote the adhesion of leukocytes ( 28 , 36 , 37 ). From this point of view, the measurement of real time leukocyte-endothelial interaction using intravital microscopy by applying a dorsal skinfold chamber is considered very important ( 30 , 38 ). Our findings suggested that both leukocyte-endothelial interactions and plasma Sdc-1 concentrations were inversely correlated with the GCX TI.…”

Fluid resuscitation with hydroxyethyl starch in perioperative acute hemorrhagic shock

“…However, the use of FFP may be limited in emergent situations since it can cause several adverse effects [23]. Recent studies have shown that fluid resuscitation with a third-generation HES (HES 130/0.4) in acute hemorrhagic shock can preserve micro-vessel integrity [8] and protect the glycocalyx layer, leading to better outcomes in animal models of acute hemorrhage [9]. Komori et al have demonstrated that fluid resuscitation with HES 130/0.4 effectively maintained adequate tissue oxygenation and peripheral perfusion compared to that with crystalloids in a rabbit model of hemorrhagic shock [8].…”

“…Their results indicated that better recovery of central venous oxygen saturation and the central venous-to-arterial carbon dioxide gap could be achieved after fluid resuscitation with HES 130/0.4. Uzawa et al also studied the efficacy of HES 130/0.4 on the microcirculation in a mouse model of acute hemorrhage [9]. They focused on modulation of the glycocalyx, which plays a crucial role in the preservation of vascular wall integrity and prevention of capillary leak, before and after fluid resuscitation in acute hemorrhagic shock.…”

“…Several studies have demonstrated that fluid resuscitation with colloids compared to crystalloids might improve the outcomes of acute hemorrhagic shock [6,7]. Moreover, recent studies have elucidated the detailed effects of fluid resuscitation with hydroxyethyl starch (HES) on microcirculation and micro-vessels in subjects with acute hemorrhagic shock [8,9]. These studies have shown that fluid resuscitation with HES can maintain adequate tissue oxygenation and peripheral perfusion [8], and suppress vascular permeability via protection of glycocalyx layer in acute hemorrhagic shock [9].…”

“…Moreover, recent studies have elucidated the detailed effects of fluid resuscitation with hydroxyethyl starch (HES) on microcirculation and micro-vessels in subjects with acute hemorrhagic shock [8,9]. These studies have shown that fluid resuscitation with HES can maintain adequate tissue oxygenation and peripheral perfusion [8], and suppress vascular permeability via protection of glycocalyx layer in acute hemorrhagic shock [9]. Conversely, many randomized controlled studies focusing on patients with septic shock have shown that the advantages of fluid resuscitation with colloids, including HES and albumin, remain controversial [10,11].…”