TRAUMA PRIMES CELLS

多器官功能衰竭（MOF）是创伤后晚期的主要原因， mortality. 我们认为细胞对炎症的反应 刺激可能受到宿主动物先前损伤的影响， 病人 因此，最初的损伤“启动”细胞，使其表现出 对随后的侮辱做出了放大的反应。 这种现象最好 例如嗜中性粒细胞的“致敏”。 我们假设 “启动”细胞。 这种引发可以将细胞反应放大到 以建设性或破坏性的方式进行后续刺激。 事实上，创伤引发了生理保护或 破坏性的程序，其临床结果是由 每次侮辱的程度和顺序。 该创伤研究中心由5个独立的项目组成， 关于第一个临床核心项目。 在临床核心中，我们 建议量化初始患者损伤的程度。 以下 初步复苏，我们计划检查高代谢“准备好” 患者以确定在此期间是否存在第二次炎性损伤 脆弱期预测MOF（项目1）。 高代谢状态 将在动物中进行研究，以确定是否有炎症 介质可以敏化（保护）和/或脱敏（损伤）β- 肾上腺素能受体偶联心肌功能（项目2）。 肠道 被认为是MOF发展的核心器官。 我们 提出损伤后肠系膜缺血/再灌注促进远端 作为循环中性粒细胞的“启动”床而造成的器官损伤 （项目3）。 与创伤相关的强烈交感神经刺激可能会“启动” 细胞代谢，以促进对随后 缺血/炎症损伤（项目4）。 最后，细胞被 损伤表达与保护相关基因的共同程序， 回收（项目5）。 在我们发展为创伤研究中心的同时，我们建议 作为创伤研究培训中心

Multiple organ failure (MOF) is the leading cause of late post-injury mortality. We propose that the cellular response to an inflammatory stimulus can be influenced by a prior injury to the host animal or patient. Thus, the initial injury "primes" cells to exhibit an amplified response to a subsequent insult. This phenomenon is best exemplified by the "priming" of neutrophils. We postulate that injury "primes" cells. this priming may amplify the cellular response to a subsequent stimulus in either a constructive or destructive fashion. Indeed, trauma initiates a race between physiologically protective or destructive programs, the clinical result of which is dictated by the magnitude and sequence of each insult. This Trauma Research Center is composed of 5 independent projects all relating to the first clinical core project. In the clinical core, we propose to quantify the magnitude of initial patient injury. Following initial resuscitation, we plan to examine the hypermetabolic "primed" patient to determine whether a second inflammatory insult during this vulnerable period predicts MOF (Project 1). The hypermetabolic state will be investigated in animals to determine whether inflammatory mediators can sensitize (protect) and/or desensitize (injure) beta- adrenergic receptor coupled myocardial function (Project 2). The gut has been invoked as an organ central to the development of MOF. We propose that post-injury mesenteric ischemia/reperfusion promotes remote organ injury by serving as a "priming" bed for circulating neutrophils (Project 3). The intense sympathetic stimulation associated with trauma may "prime" cellular metabolism to promote tolerance to subsequent ischemic/inflammatory insult (Project 4). Ultimately, cells "primed" by injury express a common program of genes which relate to protection and recovery (Project 5). Concurrent with our development as a Trauma Research Center, we propose to function as a Trauma Research Training Center.