Plasma Restoration of Endothelial Glycocalyx in a Rodent Model of Hemorrhagic Shock
ABSTRACT The use of plasma-based resuscitation for trauma patients in hemorrhagic shock has been associated with a decrease in mortality. Although some have proposed a beneficial effect through replacement of coagulation proteins, the putative mechanisms of protection afforded by plasma are unknown. We have previously shown in a cell culture model that plasma decreases endothelial cell permeability in comparison with crystalloid. The endothelial glycocalyx consists of proteoglycans and glycoproteins attached to a syndecan backbone, which together protect the underlying endothelium. We hypothesize that endothelial cell protection by plasma is due, in part, to its restoration of the endothelial glycocalyx and preservation of syndecan-1 after hemorrhagic shock.
Rats were subjected to hemorrhagic shock to a mean arterial blood pressure of 30 mm Hg for 90 minutes followed by resuscitation with either lactated Ringer's (LR) solution or fresh plasma to a mean arterial blood pressure of 80 mm Hg and compared with shams or shock alone. After 2 hours, lungs were harvested for syndecan mRNA, immunostained with antisyndecan-1, or stained with hematoxylin and eosin. To specifically examine the effect of plasma on the endothelium, we infused small bowel mesentery with a lanthanum-based solution, identified venules, and visualized the glycocalyx by electron microscopy. All data are presented as mean ± SEM. Results were analyzed by 1-way analysis of variance with Tukey post hoc tests.
Electron microscopy revealed degradation of the glycocalyx after hemorrhagic shock, which was partially restored by plasma but not LR. Pulmonary syndecan-1 mRNA expression was higher in animals resuscitated with plasma (2.76 ± 0.03) in comparison with shock alone (1.39 ± 0.22) or LR (0.82 ± 0.03) and correlated with cell surface syndecan-1 immunostaining. Shock also resulted in significant lung injury by histopathology scoring (1.63 ± 0.26), which was mitigated by resuscitation with plasma (0.67 ± 0.17) but not LR (2.0 ± 0.25).
The protective effects of plasma may be due in part to its ability to restore the endothelial glycocalyx and preserve syndecan-1 after hemorrhagic shock.
- SourceAvailable from: Timothy Pohlman
- "Shock-mediated injury of the vascular endothelium has been examined as a mechanism of TAC. This injury also includes disruption of the covering glycocalyx throughout the vascular space     . Negatively charged proteoglycans, glycoproteins, and glycolipids, including significant amounts of heparin-like molecules [65,66] of the glycocalyx have a dynamic role in a number of endothelial cell functions . "
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