Low-volume resuscitation with normal saline is associated with microvascular endothelial dysfunction after hemorrhage in rats, compared to colloids and balanced crystalloids

Abstract

BackgroundRestoration of endothelial glycocalyx (EG) barrier may be an essential therapeutic target for successful resuscitation. The aim of this study was to compare in vivo the effects of resuscitation with normal saline (NS) to lactated Ringer’s solution (LR), 5% albumin and fresh frozen plasma (FFP) on their ability to maintain EG and barrier function integrity, mitigate endothelial injury and inflammation, and restore vascular homeostasis after hemorrhagic shock.MethodsAnesthetized rats (N = 36) were subjected to hemorrhagic shock (bled 40% of total blood volume), followed by resuscitation with 45 ml/kg NS or LR, or 15 ml/kg 5% albumin or FFP. Microhemodynamics, EG thickness, permeability, leukocyte rolling and adhesion were assessed in >180 vessels from cremaster muscle, as well as systemic measures.ResultsAfter hypotensive resuscitation, arterial pressure was 25% lower than baseline in all cohorts. Unlike FFP, resuscitation with crystalloids failed to restore EG thickness to baseline post shock and shedding of glycocalyx proteoglycan was significantly higher after NS. NS decreased blood flow and shear, and markedly increased permeability and leukocyte rolling/adhesion. In contrast, LR had lesser effects on increased permeability and leukocyte rolling. Albumin stabilized permeability and white blood cell (WBC) rolling/adhesion post shock, comparable to FFP.ConclusionsResuscitation with NS failed to inhibit syndecan-1 shedding and to repair the EG, which led to loss of endothelial barrier function (edema), decline in tissue perfusion and pronounced leukocyte rolling and adhesion. Detrimental effects of NS on endothelial and microvascular stabilization post shock may provide a pathophysiological basis to understand and prevent morbidity associated with iatrogenic resuscitation after hemorrhagic shock.

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

“…This is considered to be a reliable method of measuring GCX thickness in vivo. We observed that GCX index was significantly lower in only group NS than in group C, and there were no significant differences in group NS-A and NS-V compared to group C. Consistent with the observed results for GCX thickness, the plasma concentration of syndecan-1 was significantly higher in group NS than in group C, indicating that fluid resuscitation using only normal saline leads to GCX damage [11], resulting in a poor prognosis [23][24][25].…”

Fibrinogen Protects Against Barrier Dysfunction Through Maintaining Cell Surface Syndecan-1 In Vitro

“…However, we would not anticipate other proteins to significantly participate in barrier integrity and/or not be present in human plasma in sufficient quantities to provide protection. The exception to this could be albumin, as it has been reported to provide protection to the endothelium in a rodent model of hemorrhage (30). As this study represents our initial findings into the key role of fibrinogen as an endothelial protector, future studies are needed to define the precise mechanisms for this protection.…”

Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model

“…Previously, we reported that H 2 inhalation upon induction of HS enhanced tolerance to blood loss and hemodynamic stability after fluid resuscitation with four times the shed blood volume of normal saline ( 24 ). However, that experimental protocol was inconsistent with typical clinical scenarios and the high infusion volume was harmful ( 33 , 34 ). Therefore, in this study H 2 inhalation was started after shock, mimicking H 2 inhalation in an ambulance.…”