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Plasma Components To Protect The Endothelial Barrier Following Shock: A Role For Sphingosine1-phosphate
lawrence diebel1, *David Liberati1, *Timothy Hla2, *Steven Swendeman2
1wayne state university school of medicine, detroit, MI;2Harvard School of Medicine, Boston, MA

OBJECTIVE(S): Hemorrhagic shock (HS) leads to endothelial glycocalyx (EG) shedding, endothelial cellular (EC) inflammation and increased vascular permeability. Early plasma administration improves survival in severely injured patients; this may in part be due to its ability to ameliorate this trauma induced endotheliopathy (EOT). The protective effect of early plasma administration may be due to its sphingosine 1-phosphate (S1-P) content. Principle carriers of plasma S1-P include apolipoprotein M (ApoM) and albumin. The relative roles of these carriers on S1-P protective effects are unknown and were studied in an in vitro model of microcirculation.
METHODS: Human umbilical vein endothelial cell (HUVEC) monolayers were established in microfluidic perfusion devices and subjected to control or "shock conditions" (hypoxia-reoxygenation + epinephrine, HR+Epi). In some experiments ApoM alone or loaded with S1-P, albumin S1-P or plasma were added later to the perfusate. The S1-P concentration of these solutions were adjusted to that found in plasma. At timed intervals supernatants were assayed for thrombomodulin (sTM), angiopoietin 1 and 2 (Ang-1, 2), syndecan 1 (syn-1) and heparan sulfate (HS). EG thickness was measured using fluorescent intensity.
RESULTS: Table. Mean SD, N = 6 for each group. There was no effect of ApoM or albumin alone on the studied endothelial barrier indices.
CONCLUSIONS: The S1-P component of plasma may be critical to abrogate the EOT. ApoM loaded with S1-P had the most profound effect. Carrier based S1-P may be a useful adjunct in early HS resuscitation.


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