Resuscitation with Blood Products Attenuates Endothelial Glycocalyx Shedding but not the Acute Inflammatory Response to Injury in a Military-relevant Preclinical Porcine Model of Traumatic Hemorrhagic Shock

Traumatic injury induces a complex host response, comprising endothelial damage, and simultaneous pro- and anti-inflammatory responses. These may contribute to complications seen in some patients days or weeks later. Although there is ever-increasing evidence showing that resuscitation with blood products improves survival, their impact on the host response remains unclear. A terminally anesthetized Large White pig model of traumatic hemorrhagic shock (THS) and prolonged care evaluated different resuscitation fluids (saline, fresh-frozen plasma, packed red blood cells and fresh-frozen plasma [1:1], or fresh whole blood [n = 9 per group]). Serial blood samples were collected for enzyme-linked immunosorbent assay, hematology, and flow cytometry, and postmortem tissue samples collected for RT-qPCR and immunohistochemistry. THS significantly increased circulating markers of endothelial activation (angiopoietin-2 and von Willibrand factor antigen; both P < 0.001) and glycocalyx shedding (hyaluronic acid; P < 0.001). THS also elicited a robust inflammatory response, with significant elevations in circulating interleukin-6 and high mobility group box 1 (both: P < 0.001), neutrophilia ( P < 0.001), lymphopenia ( P < 0.001), and increased inflammatory gene expression across a number of tissues. Compared with saline, resuscitation with blood products reduced hyaluronic acid ( P < 0.001) but not angiopoeitin-2 or von Willebrand factor antigen (both: P > 0.05). The effect of blood products on peripheral cytokine concentrations or immune cell populations was minimal, nor did they significantly alter tissue inflammatory gene expression, neutrophil, or lymphocyte number compared with saline-treated animals. These data suggest resuscitation with blood products can protect the endothelial glycocalyx, but they have little impact on the acute (<8 hours) host response(s) to THS and prolonged care compared to animals treated with saline.