IMPAIRED GUT TRANSIT AND HYPERTONIC SALINE RESUSCITATION

肠道运输受损和高渗盐水复苏

• 批准号: 7684663
• 负责人: FREDERICK A MOORE
• 金额: $ 21.12万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 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/7684663
• 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' 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

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

肠梗阻是一个常见的问题，有助于创伤患者谁需要积极的休克复苏的不良后果。在休克的实验室模型中，持续性肠梗阻是由缺血/再灌注（I/R）诱导的促炎症引起的。护理复苏的标准涉及用乳酸林格氏液和输血进行早期容量负荷，旨在最大限度地减少休克损伤的严重程度。然而，对于严重的电击损伤， 护理复苏导致有问题的肠水肿，并且不旨在限制I/R诱导的促炎症。高渗盐水是一个有吸引力的替代方案，因为它需要相当大的tess体积，最近的实验室研究表明，高渗盐水提供保护性抗炎作用，防止休克引起的急性肺损伤。本项目将解决以下假设：与标准治疗复苏相比，高渗盐水（含或不含胶体）将通过差异诱导局部抗炎作用而非促炎症作用，减少肠系膜I/R后的肠道损伤和转运受损。它将利用上级肠系膜动脉闭塞的标准模型，该模型已用于表征导致肠道损伤和损害肠道传输的I/R炎症。具体目标1将确定乳酸林格氏液中乳酸盐的D-异构体是否引起足够显著的促炎症，从而对肠道运输产生不利影响。具体目标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。具体目标3将使用具体目标2中确定的高渗盐水的最佳抗炎剂量，以确定高渗盐水复苏、其抗炎作用及其保护作用之间的时间关系。然后通过证明当时间相关的炎症效应被阻断时，高渗盐水复苏的保护作用被消除，来证实因果关系。然后，特定目标4将确定胶体的添加是否改变了观察到的高渗盐水复苏的抗炎作用。这些综合信息将有助于设计未来的肠道特异性复苏策略，这些策略将最大限度地减少缺血，减少有问题的水肿，并消除I/R炎症，以限制肠道损伤并加速修复