IMPAIRED GUT TRANSIT AND HYPERTONIC SALINE RESUSCITATION/PROJECT 3

肠梗阻是创伤患者需要积极休克复苏的常见问题。在实验室休克模型中，持续性肠梗阻是由缺血/再灌注（I/R）诱导的促炎症引起的。标准的护理复苏包括早期负荷乳酸林格氏液和输血，目的是尽量减少休克损伤的严重程度。然而，随着严重的休克侮辱，标准的

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