Acute hyperglycemia increases sepsis related glycocalyx degradation and endothelial cellular injury: A microfluidic study.

Hyperglycemia promotes vascular inflammation; however its effect on endothelial dysfunction in sepsis is unknown. Microfluidic devices (MFD) may closely mimic the in vivo endothelial cell microenvironment. We hypothesized that stress glucose concentrations would increase sepsis related endothelial injury/activation. Human umbilical vein endothelial cell (HUVEC) monolayers were established in microfluidic channels. TNF was added followed by glucose. Endothelial glycocalyx (EG) integrity was indexed by shedding of the EG components as well as thickness. Endothelial cell (EC) injury/activation was indexed by soluble biomarkers. Intracellular reactive oxygen species (ROS) was by fluorescence. TNF increased glycocalyx degradation and was associated with biomarkers of EC injury. These vascular barrier derangements were further increased by hyperglycemia. This may be related to increase ROS species generated followed by the combined insults. MFD technology may be a useful platform to study endothelial barrier function and stress conditions and allow preclinical assessment of potential therapies.