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Acute hyperglycemia exacerbates trauma-induced endothelial and glycocalyx injury

An in vitro model

Diebel, Lawrence N., MD; Diebel, Mark E., MD; Martin, Jonathan V., MD; Liberati, David M., MS

Journal of Trauma and Acute Care Surgery: November 2018 - Volume 85 - Issue 5 - p 960–967
doi: 10.1097/TA.0000000000001993

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 in a biomimetic in vitro model.

METHODS Human umbilical vein endothelial cell monolayers established in the microfluidic channels of a microfluidic device well plate were perfused at constant shear overnight. Human umbilical vein endothelial cell monolayers were then exposed to hypoxia/reoxygenation 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 biomimetic 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 hypoxia/reoxygenation plus epinephrine exposure and may be related to enhanced production of reactive oxygen species.

CONCLUSIONS Microfluidic device study may allow the preclinical assessment and development of therapeutic strategies of the vascular barrier under stress conditions.

From School of Medicine (L.N.D.), Wayne State University, Detroit, Michigan; and Michael and Marian Ilitch Department of Surgery (M.E.D., J.V.M., D.M.L.), Wayne State University, Detroit, Michigan.

Submitted: January 15, 2018, Revised: April 16, 2018, Accepted: May 22, 2018, Published online: May 30, 2018.

This study was presented at the 48th annual meeting of the Western Trauma Association; February 25 to March 2, 2018; Whistler, British Columbia, Canada.

Address for reprints: Lawrence N. Diebel, MD, Michael and Marian Ilitch Department of Surgery, 6C University Health Center, 4201 Saint Antoine, Detroit, MI 48201; email:

© 2018 Lippincott Williams & Wilkins, Inc.