IMPAIRED GUT TRANSIT AND HYPERTONIC SALINE RESUSCITATION/PROJECT 3
肠道运输受损和高渗盐水复苏/项目 3
基本信息
- 批准号:6813356
- 负责人:
- 金额:$ 16.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-06 至 2009-05-31
- 项目状态:已结题
- 来源:
- 关键词:antiinflammatory agentscolloidsdrug administration rate /durationgastrointestinal absorption /transportgastrointestinal disorder chemotherapygene expressionimmunogeneticsimmunoregulationinflammationintestine obstructionischemialaboratory ratlactatesmedical complicationmesenterynonhuman therapy evaluationreperfusionresuscitationsaline
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
肠梗阻是一种常见问题,会导致需要积极电击复苏的创伤患者出现不良后果。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。标准护理复苏包括早期用乳酸林格氏液进行容量负荷和输血,旨在最大程度地减少休克损伤的严重程度。然而,对于严重的休克侮辱,标准
护理复苏会导致有问题的肠道水肿,并且并非旨在限制缺血再灌注引起的促炎症。事实上,这可能会使情况变得更糟。高渗盐水是一种有吸引力的替代品,因为它需要相当大的苔藓体积,并且最近的实验室研究表明,高渗盐水可以针对休克引起的急性肺损伤提供保护性抗炎作用。该项目将解决这样的假设:与标准护理复苏相比,有或没有胶体的高渗盐水将通过差异诱导局部抗炎症而不是促炎症来减少肠道损伤和肠系膜 I/R 后的运输受损。它将利用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和损害肠道转运的 I/R 炎症。具体目标 1 将确定乳酸林格氏液中的乳酸 D 异构体是否会引起足够显着的促炎症反应,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来确定高渗盐水复苏、其抗炎作用和保护作用之间的时间关系。然后,通过证明当暂时相关的炎症效应被阻断时,高渗盐水复苏的保护作用就会被消除,从而证实因果关系。然后,具体目标 4 将确定添加胶体是否会改变观察到的高渗盐水复苏的抗炎作用。综合信息将有助于设计未来肠道特定的复苏策略,从而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其修复
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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FREDERICK A MOORE其他文献
FREDERICK A MOORE的其他文献
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{{ truncateString('FREDERICK A MOORE', 18)}}的其他基金
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脓毒症后外科 ICU 患者慢性危重疾病的流行病学
- 批准号:
8740719 - 财政年份:2014
- 资助金额:
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PICS: A New Horizon for Surgical Critical Care
PICS:外科重症监护的新视野
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8740713 - 财政年份:2014
- 资助金额:
$ 16.16万 - 项目类别:
PICS: A New Horizon for Surgical Critical Care
PICS:外科重症监护的新视野
- 批准号:
8917992 - 财政年份:2014
- 资助金额:
$ 16.16万 - 项目类别:
PICS: A New Horizon for Surgical Critical Care
PICS:外科重症监护的新视野
- 批准号:
9484296 - 财政年份:2014
- 资助金额:
$ 16.16万 - 项目类别:
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$ 16.16万 - 项目类别:
ROLE OF EARLY GUT DYSFUNCTION IN LATE POSTINJURY MOF
早期肠道功能障碍在损伤后晚期 MOF 中的作用
- 批准号:
6659285 - 财政年份:2002
- 资助金额:
$ 16.16万 - 项目类别:
ROLE OF EARLY GUT DYSFUNCTION IN LATE POSTINJURY MOF
早期肠道功能障碍在损伤后晚期 MOF 中的作用
- 批准号:
6644314 - 财政年份:2002
- 资助金额:
$ 16.16万 - 项目类别:
ROLE OF EARLY GUT DYSFUNCTION IN LATE POSTINJURY MOF
早期肠道功能障碍在损伤后晚期 MOF 中的作用
- 批准号:
6493984 - 财政年份:2001
- 资助金额:
$ 16.16万 - 项目类别:
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