J. V. Martin1, D. M. Liberati1, L. N. Diebel1 1Wayne State University,Marian And Michael Ilitch Department Of Surgery,Detroit, MI, USA
Introduction: The role of the endothelium in the regulation of hemostasis and inflammation has been recognized for some time. More recently the effect of hemorrhagic shock (HS) on endothelial dysfunction (endotheliopathy of trauma, EOT) has been described. Key factors include hypoxia and/or reactive oxygen species production and sympathoadrenal activation. However, the parameters of endothelial dysfunction and the time course of EOT are not well described. Human umbilical vein endothelial cells (HUVEC) were used to characterize EOT in vitro.
Methods: Confluent HUVEC were subjected to either control conditions (21% O2) or exposure to hypoxia (5% O2) followed by oxidant challenge (H2O2) (H/O insult), epinephrine (10-3 μM) or both H/O and epinephrine exposure. Syndecan-1 shedding was analyzed to determine glycocalyx disruption, PAI-1 and tPA were used to index coagulation profile (thrombosis and fibrinolysis, respectively). Angiopoietin-2/angiopoietin-1 ratio (APO-2/APO-1) and soluble thrombomodulin (TM) were used to index microvascular integrity and endothelial injury, respectively.
Results: See table.
Conclusion: Experimental conditions that mimic the vascular endothelial mileau following HS depict an "early" fibrinolytic profile (increased tPA) and a "later" prothrombotic profile (decreased tPA and increased PAI-1/tPA ratio). Microvascular integrity was impaired (increased APO-2/APO-1) early and remained so as did evidence of endothelial injury (TM). This study identifies temporal phenotypes of EOT and confirms an "early window" for the therapeutic use of antifibrinolytic tranexamic acid in the clinical setting.
