Effects of Damage Control Resuscitation on the Inflammatory Response to Hemorrhag

描述（由申请人提供）：拟议的职业发展奖项目将提供候选人，蒂莫西A。Pritts，MD，PhD，作为一名科学研究者，实现完全独立的工具。Pritts博士的近期和长期研究目标是成为一名独立的外科医生科学家，研究出血性休克和复苏的病理生理学。 拟议的研究项目涉及出血性休克，这是死亡和残疾的主要原因。最近的临床护理创新已被提出作为改善即时生存的尝试。这些策略被称为“损伤控制复苏”，强调血浆和红细胞的自由输血。早期的回顾性数据表明，增加血浆与红细胞的比例可降低创伤患者的即刻死亡率，但可能导致随后因多器官功能衰竭而死亡。迄今为止，没有研究检查损伤控制复苏策略与传统复苏相比对随后SIRS、器官衰竭和死亡的发展的影响。拟定的研究将使用失血性休克和复苏的小鼠模型，直接比较晶体液、全血和不同比例的血浆与红细胞复苏对全身炎症、器官衰竭和死亡的影响。 职业发展计划将涉及Alex Lentsch博士的积极指导，以及咨询委员会的监督，临床和行政活动的减少以及免疫学的额外培训。 在外科的研究环境是杰出的，设备齐全的设施和所有必要的设备来完成拟议的实验。Pritts博士得到了他的主席、部门主任和部门的全力支持。 公共卫生相关性：出血性休克是受伤患者死亡的主要原因。改善失血性休克复苏和生存的策略正在发展。这些实验将有助于了解失血性休克患者不同复苏策略的机制。

DESCRIPTION (provided by applicant): The proposed Career Development Award project will provide the Candidate, Timothy A. Pritts, MD, PhD, a vehicle to attain full independence as a scientific investigator. Dr. Pritts' immediate and long term research goals are to become an independent surgeon scientist investigating the pathophysiology of hemorrhagic shock and resuscitation. The proposed research project involves hemorrhagic shock, a major cause of death and disability. Recent innovations in clinical care have been proposed as an attempt to improve immediate survival. Termed "damage control resuscitation," these strategies emphasize liberal transfusion of plasma and red blood cells. Early retrospective data suggest that increasing ratios of plasma to red blood cells leads to decreased immediate mortality in trauma patients but may allow subsequent death from multiple organ failure. To date, there are no studies examining the impact of damage control resuscitation strategies, as compared to traditional resuscitation, on subsequent development of SIRS, organ failure, and death. The proposed studies will use a murine model of hemorrhagic shock and resuscitation to directly compare resuscitation with crystalloid fluids, whole blood, and varying ratios of plasma to red blood cells on the development of systemic inflammation, organ failure, and death. The Career Development Plan will involve active mentoring by Alex Lentsch, PhD, as well as oversight by an advisory committee, diminution of clinical and administrative activities, and additional training in immunology. The research environment in the Department of Surgery is outstanding, with well equipped facilities and all necessary equipment to complete the proposed experiments. Dr. Pritts enjoys the complete support of his Chair, his Division Director, and the Department. PUBLIC HEALTH RELEVANCE: Hemorrhagic shock is a major cause of death in injured patients. Strategies to improve resuscitation and survival from hemorrhagic shock are evolving. The proposed experiments will increase understanding of the mechanisms of different resuscitation strategies for patients who are victims of hemorrhagic shock.