ROLE OF SPLANCHNIC EICOSANOIDS DURING SHOCK

多器官衰竭(MOF)是一种严重的，通常是致命的后遗症 严重出血、败血症后内脏缺血、复苏或 在创伤之后。这项提议的总体长期目标是 是为了阐明参与调节的体液因素 出血/再灌注损伤时内脏血流的变化。这个 促进内脏血流的内源性体液因素 将研究的包括血管活性二十烷类化合物和一氧化氮(NO)。 调查的外源性体液因子包括血小板衍生 血管收缩物质和氧衍生自由基(ODFR)在 出血/再灌注损伤。我们的长期目标是调查 参与调节相关酶的特定机制 休克期间二十烷类化合物和一氧化氮的合成和降解 将为制定治疗战略作出贡献的国家 专为维持内脏血流和内脏功能而设计 接踵而至的是震惊。 急性出血后再灌流将被用作主要的 或作为初始伤害，然后进行第二次侮辱，以检查 具体目标如下：1)确定ODFR对内脏的作用 失血性休克早期二十烷类化合物的合成和一氧化氮的合成 2)确定ODFR在血管紧张素转换酶调控中的作用。 失血性休克和再灌注后内脏血流；3)至 确定局部血小板二十烷基类化合物和5-羟色胺释放的作用 失血性休克再灌流后的内脏血管床； 4)确定二次创伤(内毒素休克、出血)的作用 内脏二十烷和一氧化氮合成与内脏血流量 在最初的失血性休克之后。 这项提案将利用几种战略来确定 内脏二十烷和一氧化氮合成与内脏血流量的关系 在休克期间。第一个策略将检查以下因素的影响 内脏二十烷酸和一氧化氮的出血/再灌注损伤 合成和释放。这些研究将确定地点和 与酶调节有关的分子机制 负责内脏二十烷和一氧化氮的合成 出血/再灌注损伤。第二种策略是检查 ODFR对术后内脏血流量的影响 出血/再灌注损伤。第三个策略是研究 血小板在内脏血管收缩中的作用 通过释放5-羟色胺和血栓素来进行出血/再灌注。这个 第四种策略是确定第二次创伤的效果 (出血、内毒素、吗啡等)在内脏二十烷和 内脏血流量与一氧化氮合成的关系 大出血。

Multiple organ failure (MOF) is a serious, often fatal sequelae of visceral ischemia, resuscitation after severe hemorrhage, sepsis, or following traumatic injury. The overall long term goal of this proposal is to elucidate the humoral factors that contribute to the regulation of splanchnic blood flow during hemorrhage/reperfusion injury. The endogenous humoral factors that contribute to splanchnic blood flow that will be studied include vasoactive eicosanoids and nitric oxide (NO). The exogenous humoral factors investigated include platelet derived vasoconstrictors and oxygen-derived free radicals (ODFRs) formed during hemorrhage/reperfusion injury. Our long term goal is to investigate the specific mechanisms involved in the regulation of the enzymes responsible for eicosanoid and nitric oxide synthesis and degradation during shock states which will contribute to the development of treatment strategies designed to maintain splanchnic blood flow and visceral function following shock. Acute hemorrhage followed by reperfusion will be used either as a primary injury or as an initial injury followed by a second insult to examine the following specific aims: 1) To determine the role of ODFRs on splanchnic eicosanoid synthesis and NO synthesis following early hemorrhagic shock and reperfusion; 2) to determine the role of ODFR on the regulation of splanchnic blood flow following hemorrhagic shock and reperfusion; 3) To determine the role of local platelet eicosanoid and serotonin release in the splanchnic vascular bed following hemorrhagic shock and reperfusion; 4) To determine the role of a second trauma (endotoxin shock, hemorrhage) on splanchnic eicosanoid and NO synthesis and splanchnic blood flow following initial hemorrhagic shock. This proposal will utilize several strategies to determine the role of ODFRs on splanchnic eicosanoid and NO synthesis and splanchnic blood flow during shock. The first strategy will examine the effects of hemorrhage/reperfusion injury on splanchnic eicosanoid and nitric oxide synthesis and release. These studies will determine the location and molecular mechanisms involved with the regulation of the enzymes responsible for splanchnic eicosanoid and nitric oxide synthesis during hemorrhage/reperfusion injury. The second strategy is to examine the effects of ODFRs on splanchnic blood flow following hemorrhage/reperfusion injury. The third strategy is to examine the contribution of platelets to splanchnic vasoconstriction during hemorrhage/reperfusion by release of serotonin and thromboxane. The fourth strategy is to determine the effect of a second trauma (hemorrhage, endotoxin, morphine etc.) on the splanchnic eicosanoid and nitric oxide synthesis and splanchnic blood flow following initial hemorrhage.