Obesity and impaired barrier function after shock: A biomimetic in vitro model using microfluidics

Impaired microvascular perfusion in the obese patient has been linked to chronic adverse health consequences. The impact on acute illnesses including trauma, sepsis, and hemorrhagic shock (HS) is uncertain. Studies have shown that endothelial glycocalyx and vascular endothelial derangements are causally linked to perfusion abnormalities. Trauma and HS are also associated with impaired microvascular perfusion in which glycocalyx injury and endothelial dysfunction are sentinel events. We postulate that obesity may impact the adverse consequences of HS on the vascular barrier. This was studied in vivo in a biomimetic model of HS using microfluidic technology.

Human umbilical vein endothelial cell monolayers were established in a microfluidic device. Cells were exposed to standard or biomimetic shock conditions (hypoxia plus epinephrine) followed by perfusion from plasma obtained from obese or nonobese subjects. Endothelial glycocalyx and endothelial cellular injury were then determined.

Plasma from nonobese patients completely reversed glycocalyx and endothelial vascular barrier injury. Plasma from obese patients was only partially protective and was associated with differences in adipokines and other substances in the plasma of these patients.

Our study supports that obesity impairs HS resuscitation. This may be due to microrheological differences between nonobese and obese individuals and may contribute to the poorer outcome in this patient population.