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

Background: Restoration 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. Methods: Anesthetized 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. Results: After 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. Conclusions: Resuscitation 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.