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Effect Of Albumin Solutions On Endothelial Oxidant Injury: A Microfluidic Study
Lawrence Diebel, *David Liberati
Wayne State University School of Medicine, Detroit, MI

Objectives: Studies have suggested a beneficial effect of early plasma-based resuscitation in patients following trauma-hemorrhagic shock (T/HS). The underlying mechanism(s) are unknown but may be due to protective effects of plasma components on the endothelium and its glycocalyx layer. Albumin, the major protein in plasma, influences vascular integrity and has anti-oxidant properties in vivo. Sphingosine 1-phosphate (S1-P) is a bioactive sphingolipid with diverse signaling functions which include endothelial barrier protection in part due to preservation of the glycocalyx. S1-P is bound mainly to albumin and HDL 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 S1-P concentrations in albumin solutions on the endothelial-glycocalyx barrier in an in vitro microfluidic platform.
Methods: Human umbilical vein endothelial cell (HUVEC) monolayers were subjected to control or biomimetic shock conditions (hypoxia-reoxygenation + epinephrine) under flow followed by perfusion with 5% plasma or different albumin preparations. Albumin solutions included pharmaceutical albumin (HSA, purified by Cohn process), bovine serum albumin (BSA), and recombinant albumin (r-albumin). S1-P concentrations were determined in the different albumin solutions. Endothelial integrity was indexed by shedding of syndecan-1 (syn-1) and measurement of endothelial glycocalyx (EG) thickness. Oxidant injury was determined by protein carbonyl content and malondialdehyde (MDA). Endothelial permeability was indexed by angiopoietin-2 (Ang-2).
Results: See Table.
Conclusion: The protective effect of albumin on the endothelia-glycocalyx barrier against oxidant injury was dependent on its S1-P concentration. Our data may help explain the discrepancies regarding the effectiveness of albumin solutions in shock resuscitation.


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