Acute hyperglycemia exacerbates trauma induced endothelial and glycocalyx injury: An in vitro model

Background Early hyperglycemia is associated with higher mortality in trauma and predicts multiple organ failure. Endothelial cell (EC) injury and glycocalyx (GC) degradation occur following traumatic shock and are key factors in the development of trauma-induced coagulopathy, and result in impaired microvascular perfusion and accompanying organ failure. Acute hyperglycemia has been shown to result in the loss of the GC layer, EC inflammation, and activation of coagulation in vivo. We postulated that acute hyperglycemia would exacerbate trauma induced EC injury and GC shedding and integrity. This was studied using a microfluidic device (MFD) in a bio-mimetic in vitro model. Methods Human umbilical vein endothelial cell (HUVEC) monolayers established in the microfluidic channels of a MFD well plate were perfused at constant shear overnight. HUVEC monolayers were then exposed to hypoxia/reoxygenation (H/R) and epinephrine followed by the addition of varying concentrations of glucose. Results Glycocalyx shedding and loss of dimension as well as EC injury/activation were noted after exposure to the bio-mimetic conditions of trauma/shock in our study. Similar but less dramatic findings were noted after acute hyperglycemia. Exposure to hyperglycemia exacerbated the adverse effects on the GC and EC following H/R plus epinephrine exposure and may be related to enhanced production of reactive oxygen species (ROS). Conclusion MFD study may allow the preclinical assessment and development of therapeutic strategies of the vascular barrier under stress conditions. Level of evidence not applicable Correspondence: Lawrence N. Diebel MD, Michael and Marian Ilitch Department of Surgery, 6C University Health Center, 4201 Saint Antoine, Detroit, MI 48201, Phone: 313-577-5314, Fax: 313-577-5310. Email: ldiebel@med.wayne.edu Conflicts of interest to disclose: None This study was presented at the 48th annual meeting of the Western Trauma Association, February 25-March 2, 2018, in Whistler, British Columbia. © 2018 Lippincott Williams & Wilkins, Inc.

from Emergency Medicine via xlomafota13 on Inoreader https://ift.tt/2LNa9gr