Plasma components to protect the endothelial barrier after shock: A role for sphingosine 1-phosphate

Background: Hemorrhagic shock leads to endothelial glycocalyx shedding, endothelial cellular inflam-mation, and increased vascular permeability. Early plasma administration improves survival in severely injured patients; this may be due in part to its ability to ameliorate this trauma-induced endotheliopathy. The protective effect of early plasma administration may be due to its sphingosine 1-phosphate content. Principle carriers of plasma sphingosine 1-phosphate include apolipoprotein M and albumin. The relative roles of these carriers on sphingosine 1-phosphate protective effects are unknown and were studied in an in vitro model of microcirculation. Methods: Endothelial cell monolayers were established in microfluidic perfusion devices and exposed to control or biomimetic shock conditions. Sphingosine 1-phosphate, albumin + sphingosine 1-phosphate, or apolipoprotein M + sphingosine 1-phosphate were added later to the perfusate. Biomarkers of endothelial and glycocalyx activation and damage were then determined. Results: Sphingosine 1-phosphate preserved endothelial and glycocalyx barrier function after exposure to conditions of shock in the microcirculation. The protective effect was related to sphingosine 1 phosphate chaperones; the apolipoprotein M loaded with sphingosine 1-phosphate had the most profound effect. Conclusion: Carrier-based sphingosine 1-phosphate may be a useful adjunct in early hemorrhagic shock resuscitation. (c) 2021 Elsevier Inc. All rights reserved.