AN IN VITRO MODEL OF VASOMOTOR RELAXATION IN SEPSIS

脓毒症血管舒缩的体外模型

• 批准号: 3896253
• 负责人: R E CUNNION
• 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/3896253
• 关键词: aorta; bioassay; cardiovascular pharmacology; critical care; dogs; endotoxins; human tissue; interleukin 1; interleukin 2; laboratory rat; organ culture; shock; tumor necrosis factor alpha; vasodilatation; vasodilators

Septic shock is the leading cause of death in intensive care units in the United States. Clinical studies have shown that most patients dying of septic shock die with a state of refractory vascular collapse, i.e., a persistently low systemic vascular resistance. Many laboratories across the United States are actively engaged in attempts to elucidate the nature of the circulating substances in sepsis that underlie this vascular collapse. We have developed an in vitro model of vascular function which utilizes sections of rat thoracic aorta. These sections are precontracted with catecholamines and then exposed to sera from septic patients, sera from experimentally septic animals, or chemically purified putative mediators of sepsis. The ensuing vascular relaxation can be quantified and used as an index of activity of these substances. Ongoing studies have established that (1) both human and canine septic sera possess potent vascular depressant effects, (2) many of the putative mediators of sepsis (including endotoxin, interleukin-1, and interleukin-2) do not have vascular depressant effects, (3) the mediator TNF (tumor necrosis factor) produces vascular depression in a dose-dependent fashion which relies in part on the presence of an intact endothelium, and (4) the vascular depressant activity in human septic sera is not dialyzable and is not attenuated with pretreatment with anti-TNF antisera. Continuing efforts are aimed at the isolation and characterization of sepsis-related vascular depressant substances, which have importance to both our understanding of the pathophysiology of sepsis and our ability to reverse the manifestations of sepsis with appropriate immunotherapeutic agents.

在美国，感染性休克是重症监护病房死亡的主要原因。 美国的 临床研究表明，大多数死于 败血性休克死亡时会出现顽固性血管萎陷，即，一 全身血管阻力持续偏低。 许多实验室在 美国正积极地试图阐明 败血症中的循环物质， 崩溃 我们已经开发了一种血管功能的体外模型， 大鼠胸主动脉切片。 这些部分与 然后暴露于脓毒症患者的血清， 实验性脓毒症动物，或化学纯化的假定介质， 败血症 随后的血管舒张可以量化并用作 这些物质的活性指数。 正在进行的研究已经确定：（1）人和犬的脓毒症血清 具有强有力的血管扩张作用，（2）许多假定的 脓毒症介质（包括内毒素、白细胞介素-1和白细胞介素-2） 没有血管扩张作用，（3）介质TNF（肿瘤 坏死因子）以剂量依赖性方式产生血管抑制 其部分依赖于完整内皮的存在，以及（4） 人脓毒症血清中的血管活性是不可透析的， 用抗TNF抗血清预处理未减毒。 继续努力的目的是分离和定性 脓毒症相关的血管炎物质，这些物质对 我们对脓毒症病理生理学的理解和我们 用适当的免疫疗法逆转脓毒症的表现 剂.