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为候选人Timothy A.Pritts，医学博士，获得完全独立的科学研究人员提供一个工具。普里茨博士的近期和长期研究目标是成为一名独立的外科科学家，研究失血性休克和复苏的病理生理学。拟议的研究项目涉及失血性休克，这是导致死亡和残疾的主要原因。最近在临床护理方面的创新被提出为试图改善近期存活率。这些策略被称为“损害控制复苏”，强调自由输注血浆和红细胞。早期的回顾数据表明，增加血浆和红细胞的比例可以降低创伤患者的即时死亡率，但可能会导致随后的多器官衰竭死亡。到目前为止，还没有研究表明与传统复苏相比，损伤控制复苏策略对SIRS的后续发展、器官衰竭和死亡的影响。这项拟议的研究将使用失血性休克和复苏的小鼠模型，直接比较复苏与晶状液、全血和不同比例的血浆和红细胞在全身炎症、器官衰竭和死亡方面的发展。职业发展计划将包括Alex Lentsch博士的积极指导，以及咨询委员会的监督，减少临床和行政活动，以及额外的免疫学培训。外科的研究环境很好，有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、他的部门主任和该部的全力支持。 公共卫生相关性：失血性休克是受伤患者死亡的主要原因。改善失血性休克的复苏和存活率的战略正在演变。拟议的实验将增加对失血性休克患者不同复苏策略的机制的理解。

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.