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.
J Trauma Acute Care Surg. 2018 Nov;85(5):960-967. doi: 10.1097/TA.0000000000001993.
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.
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.
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.
Microfluidic device study may allow the preclinical assessment and development of therapeutic strategies of the vascular barrier under stress conditions.
创伤后早期高血糖与死亡率升高相关，并预测多器官衰竭。创伤性休克后内皮细胞（EC）损伤和糖萼（GC）降解，是创伤性凝血病发展的关键因素，导致微血管灌注受损和伴随的器官衰竭。急性高血糖已被证明会导致 GC 层丢失、EC 炎症和体内凝血激活。我们推测急性高血糖会加重创伤引起的 EC 损伤和 GC 脱落及完整性受损。这是在仿生体外模型中使用微流控装置进行的研究。
在微流控装置的微孔板微流控通道中建立的人脐静脉内皮细胞单层在恒剪切力下过夜灌注。然后，将人脐静脉内皮细胞单层暴露于缺氧/复氧和肾上腺素，然后加入不同浓度的葡萄糖。
在本研究中，我们发现暴露于创伤/休克的仿生条件后，GC 脱落和尺寸丢失以及 EC 损伤/激活。在急性高血糖后也发现了类似但不那么明显的发现。暴露于高血糖会加剧缺氧/复氧加肾上腺素暴露后对 GC 和 EC 的不利影响，这可能与活性氧的产生增强有关。
微流控装置研究可能允许在应激条件下对血管屏障进行临床前评估和治疗策略的开发。
