Endothelial dysfunction in areas of unburned skin in a burn injury model

Abstract

Introduction

Burn shock is mediated by a complex inflammatory response leading to endothelial cell dysfunction (EnD) and increased vascular permeability in large total body surface area (TBSA) injuries. Smaller TBSA burns do not induce systemic EnD. Previous studies in animal models have examined systemic markers of endothelial cell dysfunction following thermal injury and have aimed to characterize this dysfunction in various end organs. However, there is limited literature investigating EnD in the intact, unburned skin in burn patients. Intact skin with compromised microvasculature could lead to un-intended consequences during the process of achieving definitive wound closure. For this reason, we aimed to examine the presence of EnD in the unburned skin of burn injured animals.

Methods

Sprague-Dawley rats underwent thermal burn injury creation or sham procedures. Rats were subjected to 40 % TBSA scald burn, after which they were resuscitated with crystalloid (LR), LR+ early fresh frozen plasma (FFP), LR+late FFP, or LR+early albumin, and monitored for 24 h. At necropsy, Evans blue dye (EBD) was administered to assess vascular permeability and samples of healthy, unburned, intact skin were assessed using spectrophotometry. One-way ANOVA with multiple comparisons was used to compare groups. Intact skin was stained with antibodies to syndecan-1 (SDC-1), a component of the endothelial glycocalyx.

Results

EBD extraction was significantly higher in the intact skin of all 40 % TBSA injured animals (n = 17) vs. all control uninjured animals (n = 12) (p < 0.05). The largest EBD extravasation was exhibited in animals that were resuscitated with LR alone. Compared to LR alone, early administration of FFP as an adjunct to LR significantly lowered the EBD levels (p < 0.0001). Early administration of albumin did the same (p < 0.05), but not to the same degree as the early FFP. Late administration of FFP at hour 8 did not ameliorate permeability (p > 0.05). There was a significant increase in SDC-1 staining intensity in the burn LR+FFP groups compared to the burn LR group (p < 0.05) indicating more intact and less shed SDC-1.

Conclusions

EnD is evident in the unburned skin of thermally injured rats based on a vascular permeability assay. Early administration of FFP led to amelioration of EnD in the unburned skin.