IMPAIRED GUT TRANSIT AND HYPERTONIC SALINE RESUSCITATION

肠道运输受损和高渗盐水复苏

基本信息

批准号：
7502006
负责人：
FREDERICK A MOORE
金额：
$ 30.32万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7502006
关键词：
Abdomen Acute Lung Injury Address Affect Anti-Inflammatory Agents Anti-inflammatory Apoptosis Appendix Blood Blood Banks Blood Plasma Volume Blood Transfusion Blood flow Brain Cardiac Output Caring Cell Adhesion Molecules Clinical Colloids Compartment syndromes Complex Complication Dextrans Distant Dose Early Intervention Edema Effector Cell Endothelial Cells Endotoxins Enteral Nutrition Enzymes Erythrocytes Family Functional disorder Future Gene Expression Genes Hemorrhagic Shock Hetastarch IL8 gene Ileus In Vitro Inflammation Inflammatory Inflammatory Response Inflammatory disease of the intestine Injury Intercellular adhesion molecule 1 Interleukin-1 Intestines Intracranial Hypertension Ischemia Isomerism Isotonic Exercise Laboratories Laboratory Study Lactated Ringer&apos s Solution Life Link Liquid substance Lung Lymph Mediator of activation protein Melanocyte stimulating hormone Mesenteric Arteries Mesentery Mitogen-Activated Protein Kinases Modeling Multiple Organ Failure Necrosis Organ Outcome Oxidants Oxygen Pathogenesis Patients Perfusion Phospholipase A2 Physiological reperfusion Play Protein Kinase Proteins Purpose Reperfusion Injury Reperfusion Therapy Research Personnel Resuscitation Risk Risk Factors Role Saline Sepsis Sepsis Syndrome Severities Shock Standards of Weights and Measures Sterility Stress Swelling Tissues Toxin Trauma Upper digestive tract structure Vasodilation artery occlusion chemokine crystalloid cyclooxygenase 2 cytokine cytotoxicity design dextran experience heme oxygenase-1 human NOS2A protein improved in vivo interest lipid mediator natural hypothermia neutrophil pathogen prevent protective effect repaired response vasoconstriction

项目摘要

Ileus is a common problem that contributes to adverse outcome in trauma patients who require aggressive shock resuscitation. In laboratory models of shock, persistent ileus is caused by ischemia/reperfusion (I/R) induced pro-inflammation. Standard of care resuscitation which involves early volume loading with lactated Ringer's and blood transfusions is directed at minimizing the severity of the shock insult. However, with severe shock insults, standard of care resuscitation causes problematic gut edema and is not directed at limiting I/R induced pro-inflammation. In fact, it may worsen it. Hypertonic saline is an attractive alternative because it requires considerable tess volume and recent laboratory studies have shown that hypertonic saline provides protective anti-inflammation against shock induced acute lung injury. This project will address the HYPOTHESIS that hypertonic saline, with or without a colloid compared to standard of care resuscitation, will decrease gut injury and impaired transit after mesenteric I/R by differentially inducing local anti-inflammation over pro-inflammation. It will utilize a standard model of superior mesenteric artery occlusion that has been used to characterize I/R inflammation that causes gut injury and impairs intestinal transit. Specific Aim 1 will determine whether the D-isomer of lactate in lactated Ringer's causes pro-inflammation significant enough to adversely effect intestinal transit. Specific Aim 2 will determine the dose response relationship between hypertonic saline resuscitation and its anti-inflammatory protective effects. Specific Aim 3 will use the optimal anti-inflammatory dose(s) of hypertonic saline identified in Specific Aim 2 to determine the temporal relationship between hypertonic saline resuscitation, its anti-inflammatory effects and its protective effects. Causal relationship will then be confirmed by demonstrating that when temporally related inflammatory effects are blocked, the protective effects of hypertonic saline resuscitation are abrogated. Specific Aim 4 will then determine if the addition of the colloid modifies the observed anti-inflammatory effects of hypertonic saline resuscitation. The combined information will help design future gut specific resuscitation strategies that will minimize ischemia, reduce problematic edema, and abrogate I/R inflammation to limit gut injury and hasten its repair

肠病是一个常见的问题，会导致需要积极休克复苏的创伤患者的不良结果。在冲击实验室模型中，持续的肠病是由缺血/再灌注（I/R）引起的促炎引起的。护理复苏标准涉及带有乳酸和输血的早期体积加载，目的是最大程度地减少冲击侮辱的严重程度。但是，由于严重的冲击侮辱，标准护理复苏会导致有问题的肠道水肿，并且并非限制I/R引起的促炎。实际上，它可能会使它恶化。高渗盐水是一种有吸引力的替代方法，因为它需要相当大的苔丝体积，而最近的实验室研究表明，高渗盐水可为休克诱导的急性肺损伤提供保护性抗炎。该项目将解决以下假设：与护理标准复苏相比，高渗盐水或没有胶体的高渗盐水将通过差异诱导促炎促炎的局部抗炎，从而减少肠道损伤和肠内I/R的过境受损。它将利用上肠系膜上动脉闭塞的标准模型，该模型已用于表征导致肠道损伤并损害肠道转运的I/R炎症。具体的目标1将确定乳酸林格的乳酸的D-异构体是否引起促炎的促炎，足以对肠道转移产生不利影响。特定的目标2将确定高渗盐水复苏与其抗炎保护作用之间的剂量反应关系。特定目标3将使用特定目标2中鉴定出的高渗盐水的最佳抗炎剂量来确定高渗盐水复苏，其抗炎作用及其保护作用之间的时间关系。然后，将通过证明在暂时相关的炎症作用被阻断时，就会确认因果关系，高渗盐水复苏的保护作用被废除。然后，特定的目标4将确定添加胶体是否会修饰观察到的高渗盐复苏的抗炎作用。合并的信息将有助于设计未来的肠道复苏策略，以最大程度地减少缺血，减少问题性水肿并消除I/R炎症以限制肠道损伤并加速其修复