Background: Studies have suggested a beneficial effect of early plasma-based resuscitation in patients following trauma-hemorrhagic shock. The underlying mechanism(s) are unknown but may be owing to protective effects of plasma components on the endothelium and its glycocalyx layer. Albumin, the major protein in plasma, influences vascular integrity and has antioxidant properties in vivo. Sphingosine 1-phosphate is a bioactive sphingolipid with diverse signaling functions, which include endothelial barrier protection in part owing to preservation of the glycocalyx. Sphingosine 1-phosphate is bound mainly to albumin and high-density lipids in the plasma. Debate continues about the beneficial effect of albumin solutions in shock resuscitation. Pharmacologic preparations may modify constituents of albumin solutions for clinical use. We examined the relative effects of sphingosine 1-phosphate concentrations in albumin solutions on the endothelial-glycocalyx barrier in an in vitro microfluidic platform.
Methods: Endothelial cell monolayers were established in microfluidic perfusion devices and exposed to control or biomimetic shock conditions followed by 5% plasma or different albumin solutions ± exogenous sphingosine 1-phosphate perfusion. Biomarkers of endothelial and glycocalyx activation, damage, and oxidant injury were then determined.
Results: Endothelial cell and glycocalyx barriers were damaged after biomimetic shock conditions. Plasma and sphingosine 1-phosphate loaded albumin solutions protected against barrier injury. Modest protective effects were noted with albumin alone; the efficacy varied with sphingosine 1-phosphate content of the albumin solution.
Conclusion: The protective effect of albumin on the endothelia-glycocalyx barrier against oxidant injury was dependent on its sphingosine 1-phosphate concentration. Our data may help explain the discrepancies regarding the effectiveness of albumin solutions in shock resuscitation.
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