Hamilton Gregory J, Van Philbert Y, Differding Jerome A, Kremenevskiy Igor V, Spoerke Nicholas J, Sambasivan Chitra, Watters Jennifer M, Schreiber Martin A
Division of Trauma, Critical Care & Acute Care Surgery, Department of Surgery, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
J Trauma. 2011 Aug;71(2):292-7; discussion 297-8. doi: 10.1097/TA.0b013e31821f4234.
Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown.
Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals.
No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p < 0.05), but less so at 2 hours in the AA group compared with CA and HCl.
In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.
对于需要大量输血的患者，给予高比例的血浆与红细胞悬液可提高生存率。失血性休克会导致促炎细胞因子的产生增加。这些因子与后期的发病率和死亡率相关。使用新鲜冰冻血浆进行高比例复苏在后勤方面存在困难，且无法解决炎症功能障碍问题。冻干血浆（LP）是一种稳定的粉末状血浆，既安全又易于复溶。先前的研究表明，用抗坏血酸（AA）复溶的LP可减轻炎症。炎症的减轻是与LP还是与AA相关尚不清楚。
对30只雌性猪进行麻醉，并使其经历一个多系统战斗相关模型，包括股骨骨折、控制性出血和体温过低。造成标准化的V级肝损伤，然后将动物随机分配接受用AA、柠檬酸（CA）或盐酸（HCl）复溶的LP。在基线、2小时和4小时采集血液，通过酶联免疫吸附测定法测量白细胞介素（IL）-6、IL-8和肿瘤坏死因子-α的血清浓度。在对动物实施安乐死之前，采集肺组织并进行基因表达检测。
在死亡率、基线细胞因子血清浓度或基因表达方面未观察到差异。酶联免疫吸附测定法表明，所有组的IL-6浓度均随时间增加（p < 0.05），但与CA组和HCl组相比，AA组在2小时时增加较少。
在这个创伤、出血和复苏的动物模型中，相对于CA和HCl，AA可降低IL-6的表达。这些发现证实了我们实验室先前的研究结果，并表明在该模型中AA是抑制炎症功能障碍的原因。
