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.

前言和目的：脓毒性休克是一种由严重的、压倒性的感染引起的高致死性综合征。这种情况是美国重症监护室死亡的主要原因。尽管经过了半个世纪的科学研究，但导致这种综合征的潜在机制仍不完全清楚。 这些研究旨在研究脓毒性休克的发病机制，并探索新的治疗策略的潜力，使用小和大的模型的综合征，脓毒症患者，和正常志愿者挑战内毒素。 建议的工作路线： 正在进行的脓毒性休克常用血管加压药（包括肾上腺素、去甲肾上腺素和血管加压素）的生存率比较研究。 淋巴细胞过继性转移和主动脉内球囊反搏支持治疗感染性休克的方案正在开发中。 研究脓毒症患者的下丘脑-垂体-肾上腺轴，以及低剂量糖皮质激素替代治疗提高脓毒症休克患者生存率的机制。 收集和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。