Hypertonic Modulation of Inflammation following Injury

损伤后炎症的高渗调节

基本信息

批准号：
7625093
负责人：
EILEEN M BULGER
金额：
$ 37.77万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-11 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7625093
关键词：
Adenosine Animal Model Anti-Inflammatory Agents Anti-inflammatory Apoptosis Blinded Blood specimen Canada Cell Adhesion Molecules Cell Surface Receptors Cell physiology Cells Clinical Cytoskeleton Development Dextran 70 Dextrans Enrollment Equilibrium Functional disorder Funding Human Hypovolemic Shock Immune Immune System Diseases Immune system Immunologics Immunosuppression In Vitro Infection Inflammation Inflammatory Inflammatory Response Injury Investigation Laboratories Liquid substance Multi-Institutional Clinical Trial Multiple Organ Failure Neutrophil Activation Normal saline Nosocomial Infections Organ Organ failure Outcome Patients Phenotype Population Production Protocols documentation Randomized Controlled Clinical Trials Research Personnel Resuscitation Risk Saline Sepsis Shock Signal Transduction Site T-Lymphocyte Therapeutic Uses Time Trauma Traumatic Brain Injury United States National Institutes of Health Universities Upper arm Washington base clinical research site crystalloid cytokine dextran in vivo monocyte mortality neutrophil prevent programs research study response response to injury restoration toll-like receptor 4 trial comparing

项目摘要

DESCRIPTION (provided by applicant): This is a proposal to determine the effect of prehospital hypertonic resuscitation vs. conventional resuscitation with crystalloid on the inflammatory response early after injury. The leading cause of late mortality following injury is multiple organ dysfunction syndrome, which results from dysfunctional inflammatory response of the patient early after injury. Previous studies, suggest that hypertonic saline may be beneficial in modulating this initial response and thus decrease the subsequent organ injury. These effects, which have been well described in the laboratory, have yet to be proven in humans, particularly in the setting of severe injury. This proposal takes advantage of a unique opportunity to obtain blood samples from patients enrolled in a NIH supported multi-center trial of hypertonic resuscitation and analyze their inflammatory responses early after injury. The proposed trial is to be conducted by the Resuscitation Outcomes Consortium (ROC), which consists often clinical centers in the US and Canada. This study is a three arm, blinded, randomized trial comparing 7.5% saline, 7.5% saline/6% dextran-70 and normal saline (0.9%) as the initial resuscitation fluid administered to patients in hypovelemic shock or with signs of sever traumatic brain injury. Three of the ROC clinical sites will collaborate to study then inflammation response of patients enrolled at theses sites. The specific aims include: Aim 1: To profile and characterize the phenotype of the innate and cellular immune systems in response to hypertonic resuscitation following injury. Aim 2: To define, in humans, the cellular mechanisms responsible for hypertonic modulation of the inflammatory response. Aim 3: To determine whether immunologic changes observed following hypertonic resuscitation associated with differences in clinical outcome as manifested by the development of organ dysfunction, and nosocomial infection. The results of these studies will provide valuable information to determine the ultimate therapeutic use of the resuscitation strategy.

描述（由申请人提供）：这是一项建议，旨在确定院前高渗复苏与晶体复苏对晶体的效果的影响。损伤后晚期死亡率的主要原因是多发性器官功能障碍综合征，这是由于受伤后早期患者的炎症反应引起的。先前的研究表明，高渗盐水可能有益于调节这种初始反应，从而减少随后的器官损伤。这些在实验室中已经很好地描述的影响在人类中尚未得到证明，特别是在严重伤害的情况下。该提案利用了独特的机会，从参加NIH支持的高渗复苏的多中心试验的患者中获取血液样本，并在受伤后早期分析其炎症反应。拟议的试验将由复苏结果联盟（ROC）进行，该试验通常由美国和加拿大的临床中心组成。这项研究是一项三臂，盲目的随机试验，比较7.5％盐水，7.5％盐水/6％葡萄糖-70和正常盐水（0.9％），作为对低流血性休克患者施用的初始复苏液或具有少脑部外伤的迹象。 ROC的三个临床部位将协作研究，然后在这些部位入学的患者的炎症反应。具体目的包括：目标1：以响应损伤后的高渗复苏，构造和表征先天和细胞免疫系统的表型。目标2：在人类中定义负责炎症反应高渗调节的细胞机制。目的3：确定在与临床结果差异相关的高渗复苏后观察到的免疫学变化是否由器官功能障碍的发展和性交感染所表现出来。这些研究的结果将提供有价值的信息，以确定复苏策略的最终治疗使用。