Endothelial dysfunction is dampened by early administration of fresh frozen plasma in a rodent burn shock model

啮齿动物模型 休克(循环) 啮齿动物 内皮功能障碍 医学 麻醉 内科学 生物 生态学
作者
Edward J. Kelly,Eriks Ziedins,Bonnie C. Carney,Lauren T. Moffatt,Jeffrey W. Shupp
出处
期刊:The journal of trauma and acute care surgery [Ovid Technologies (Wolters Kluwer)]
标识
DOI:10.1097/ta.0000000000004373
摘要

ABSTRACT Background Endothelial dysfunction has been implicated in the pathogenesis of burn shock affecting patients with large thermal injury. In response to injury, glycocalyx components like Syndecan-1 (SDC-1) are shed into circulation and have been used as markers of endothelial damage. Previous work in our lab has shown plasma inclusive resuscitation (PIR) with fresh frozen plasma (FFP) ameliorates endothelial damage. However, there remains a paucity of information regarding optimal timing and dosing of PIR as well as organ specific endothelial responses to shock. We aimed to examine the impact of PIR on endothelial dysfunction using clinically-translatable timing and dosing. Methods Spraque-Dawley rats were used to create thermal burns. Rats were subjected to 40% TBSA scald burns and were resuscitated with LR only, LR + albumin and LR + early 1 ml boluses of FFP at 0,2,4 and 8 hours post-injury. A late group also received LR + FFP starting at hour 10 post-injury. SDC-1 levels were quantified by ELISA and qRT-PCR analysis characterized transcription of glycocalyx components and inflammatory cytokines in the lung and spleen. Evan’s blue dye (EBD) was used to quantify amount of vascular leakage. Results LR + early FFP reduced EBD extravasation when compared to LR only groups while late FFP did not. When comparing LR only vs LR + early FFP, SDC-1 levels were reduced in the LR + early FFP group at hour 8, 12 and 24 (5.23 vs. 2.07, p < 0.001, 4.49 vs. 2.05, p < 0.01, 3.82 vs 2.08, p < 0.05, respectively). LR only groups had upregulation of Exostosin-1 (EXT-1) and SDC-1 in the lung compared to LR + early FFP groups (p < 0.01 and p < 0.05) as well as upregulation of cytokines IL-10 and IFN-Ƴ (p < 0.001 and p < 0.001). Conclusions Early administration of LR + FFP reduces the magnitude of SDC-1 shedding and dampens the cytokine response to injury. The upregulation of glycocalyx components as a response to endothelial injury is also decreased in the lung and spleen by LR + early FFP administration.
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