应用VitC减轻猪多发伤凝血病和炎症的实验研究
Interventional Vitamin C: A Strategy for Attenuation of Coagulopathy and Inflammation in a Swine Polytrauma Model
Penny S. Reynolds,et-al.
Department of Anesthesiology; Virginia Common wealth University Medical Center, Richmond, Virginia, United States of America
Journal of Trauma and Acute Care Surgery,DOI: 10.1097/TA.0000000000001844
摘要
背景：
出血性休克和创伤损伤引起的凝血病和炎症与发病率和死亡率的增长有关。维生素C是在促炎和促凝通路上具有较强保护作用的抗氧化剂。我们拟在猪多发伤和出血模型伤验证液体复苏时给予高剂量VitC 是否可以减轻炎症、凝血障碍和终末器官功能损害。
Abstract
BACKGROUND Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the pro-inflammatory and pro-coagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of polytrauma and hemorrhage.
方法：
将公猪（24只，平均体重27kg）麻醉、插管、机械通气后连接监护仪进行生理学监测。对猪进行创伤性损伤/休克的干预（低体温、肝缺血再灌注、股骨粉碎性骨折、出血性低血压），随后进行500mL羟乙基淀粉液体复苏，并随机接受静脉生理盐水、低剂量VitC（50mg/kg; LO）或高剂量VitC (200 mg/kg; HI)。复苏后4h进行血流动力学、血生化、血液学和凝血功能（ROTEM）检测，并对肝、肾、肺进行组织学和分子检测
METHODS Male Sinclair swine (n = 24; meanbody weight 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiological monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500mL of hydroxyethyl starch, and randomized to receive either intravenous saline (NS), low dose VitC (50mg/kg; LO), or high dose VitC (200 mg/kg; HI).Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours post-resuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung.
结果：
与应用Vit C的动物相比，生理盐水组的猪组织学检查显示出显著的终末期器官损害，急性肺损伤评分明显升高，组织促炎因子(IL-1, IL-8, TNF)、PAI-1和TF均显著升高。VitC治疗组之间的平均动脉压和凝血功能没有区别，生理盐水组在术后4h表现为明显的凝血功能损害。
RESULTS
Compared to VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue pro-inflammatory mediators(IL-1, IL-8, TNF), PAI-1, and TF. There were no statistically significant differences between treatment groups on MAP or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours.
结论：
尽管凝血功能障碍的纠正是适度的，静脉高剂量Vit C 可以缓解严重多发伤后继发的促炎促凝反应，从而减轻多器官功能衰竭。
CONCLUSIONS Although correction ofcoagulation dysfunction was modest, intravenous high-dose VitC may mitigate the pro-inflammatory/pro-coagulant response that contributes to multiple organfailure following acute severe polytrauma.
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