Preclinical and Clinical Investigations in Septic Shock

感染性休克的临床前和临床研究

• 批准号: 7215797
• 负责人: ROBERT L DANNER
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7215797
• 关键词: antiinflammatory agents; aortic balloon pump; biomarker; dogs; drug screening /evaluation; endotoxins; epinephrine; glucocorticoids; human subject; human therapy evaluation; hypothalamic pituitary adrenal axis; ibuprofen; nitric oxide; norepinephrine; passive immunization; pathologic process; patient oriented research; pneumonia; respirators; septic shock; vasodilation; vasopressins

Introduction and Objective: Septic shock is a highly lethal syndrome initiated by severe, overwhelming infection. This condition is the leading cause of death in Intensive Care Units in the U.S. The underlying mechanisms that cause this syndrome remain incompletely understood despite more than a half century of scientific investigation. These studies seek to examine septic shock pathogenesis and to explore the potential of novel therapeutic strategies using both small and large models of the syndrome, patients with sepsis, and normal volunteers challenged with endotoxin. Proposed Course of Work: Ongoing comparative survival study of commonly used vasopressors in septic shock including epinephrine, norepinephrine and vasopressin. Protocols under development for lymphocyte adoptive transfer, and intra-aortic balloon pump support in septic shock. Investigate the hypothalmic-pituitary-adrenal axis in sepsis and the mechanisms by which low dose glucocorticoid replacement therapy improves survival in septic shock. Validate and apply information on biomarkers and pathogenic pathways obtained from functional genomic investigations.

简介和目的：感染性休克是一种由严重、压倒性感染引发的高度致命的综合征。这种情况是美国重症监护病房死亡的主要原因。尽管经过半个多世纪的科学研究，导致这种综合征的潜在机制仍未完全了解。 这些研究旨在检查感染性休克的发病机制，并利用小型和大型的综合征模型、脓毒症患者和受到内毒素挑战的正常志愿者来探索新的治疗策略的潜力。 拟议的工作过程： 正在进行的败血性休克常用升压药（包括肾上腺素、去甲肾上腺素和升压素）的比较生存研究。 正在开发淋巴细胞过继转移和主动脉内球囊反搏泵支持感染性休克的方案。 研究脓毒症中的下丘脑-垂体-肾上腺轴以及低剂量糖皮质激素替代疗法提高脓毒症休克生存率的机制。 验证并应用从功能基因组研究中获得的生物标志物和致病途径的信息。