Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia.
Department of Pharmaceutics, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia.
J Thromb Haemost. 2019 Nov;17(11):1827-1837. doi: 10.1111/jth.14580. Epub 2019 Aug 25.
Fluid resuscitation plays a prominent role in stabilizing trauma patients with hemorrhagic shock yet there remains uncertainty with regard to optimal administration time, volume, and fluid composition (e.g., whole blood, component, colloids) leading to complications such as trauma-induced coagulopathies (TIC), acidosis, and poor oxygen transport. Synthetic fluids in combination with antioxidants (e.g., vitamin C) may resolve some of these problems.
We applied quantitative mass spectrometry-based proteomics [liquid chromatography-mass spectrometry (LC-MS/MS)] to map the effects of fluid resuscitation and intravenous vitamin C (VitC) in a pig model of polytrauma (hemorrhagic shock, tissue injury, liver reperfusion, hypothermia, and comminuted bone fracture). The goal was to determine the effects of VitC on plasma protein expression, with respect to changes associated with coagulation and trauma-induced coagulopathy (TIC).
Longitudinal blood samples were drawn from nine male Sinclair pigs at baseline, 2 h post trauma, and 0.25, 2, and 4 h post fluid resuscitation with 500 mL hydroxyethyl starch. Pigs were treated intravenously (N = 3/treatment group) with saline, 50 mg VitC/kg (Lo-VitC), or 200 mg VitC/kg (Hi-VitC) during fluid resuscitation.
A total of 436 plasma proteins were quantified of which 136 changed following trauma and resuscitation; 34 were associated with coagulation, complement cascade, and glycolysis. Unexpectedly, Lo-VitC and Hi-VitC treatments stabilized ADAMTS13 levels by ~4-fold (P = .056) relative to saline and enhanced ADAMTS13/von Willebrand factor (VWF) cleavage efficiency based on LC-MS/MS evidence for the semitryptic VWF cleavage product (VWF ).
This study provides the first comprehensive map of trauma-induced changes to the plasma proteome, especially with respect to proteins driving the development of TIC.
液体复苏在稳定失血性休克创伤患者方面起着重要作用，但在最佳给药时间、容量和液体成分（例如全血、成分、胶体）方面仍存在不确定性，导致创伤诱导的凝血障碍 (TIC)、酸中毒和氧气输送不良等并发症。合成液与抗氧化剂（如维生素 C）联合使用可能会解决其中一些问题。
我们应用基于定量质谱的蛋白质组学（液相色谱-质谱联用技术，LC-MS/MS）来绘制液体复苏和静脉注射维生素 C（VitC）在多创伤猪模型（失血性休克、组织损伤、肝脏再灌注、低体温和粉碎性骨折）中的作用。目的是确定 VitC 对血浆蛋白表达的影响，特别是与凝血和创伤诱导的凝血障碍 (TIC) 相关的变化。
从 9 只雄性 Sinclair 猪的基线、创伤后 2 小时和液体复苏后 0.25、2 和 4 小时取纵向血样，液体复苏使用 500 mL 羟乙基淀粉。在液体复苏期间，猪静脉内（N=3/治疗组）分别给予生理盐水、50mg/kg VitC（低 VitC）或 200mg/kg VitC（高 VitC）。
共定量了 436 种血浆蛋白，其中 136 种在创伤和复苏后发生变化；34 种与凝血、补体级联和糖酵解有关。出乎意料的是，与生理盐水相比，低 VitC 和高 VitC 治疗使 ADAMTS13 水平稳定约 4 倍（P=0.056），并根据 LC-MS/MS 证据增强 ADAMTS13/血管性血友病因子（VWF）的切割效率，即半酶切 VWF 切割产物（VWF）。
本研究首次全面绘制了创伤诱导的血浆蛋白质组变化图谱，特别是与导致 TIC 发展的蛋白质有关。
