STUDIES OF SEPSIS UTILIZING SPONTANEOUSLY BEATING MYOCYTES IN TISSUE CULTURE

利用组织培养中自发搏动心肌细胞进行脓毒症的研究

• 批准号: 3896251
• 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/3896251
• 关键词: bioassay; dogs; heart cell; heart contraction; heart pharmacology; human tissue; laboratory rat; shock; single cell analysis; tissue /cell culture; video recording system

Myocardial dysfunction in sepsis has been a central research focus of the Critical Care Medicine Department over the past 8 years. Clinical studies of myocardial function are limited by the confounding effects of changes in preload and afterload on ventricular function. The use of single myocytes in tissue culture has the major advantage of allowing assessment of contractility independent of changes in loading conditions. A system has been developed which utilizes spontaneously beating newborn rat myocytes, which are grown in Petri dishes, imaged under a phase- contrast microscope, linked to a television monitoring system, and data fed to an analytic system capable of quantitating the amplitude and velocity of myocyte contraction. Using this system it has been demonstrated that sera from septic patients depresses myocyte contraction in close quantitative and temporal association with the depression of left ventricular ejection fraction seen in vivo. Accordingly, we have sought to isolate and characterize this myocardial depressant substance (or substances) from human and from septic canine specimens; it appears to be a novel molecule with a molecular weight of greater than 10K daltons. The known mediators of sepsis (i.e., endotoxin, interleukins 1 and 2, and tumor necrosis factor) have been screened using the in vitro assay. The incidence of myocardial depressant activity has been assayed in a large clinical series of septic shock patients and found to be approximately 40%. It is hoped that specific identification of these myocardial depressant substances will lead directly to the creation of new therapeutic modalities for sepsis.

脓毒症时的心肌功能障碍一直是研究的中心。 重症监护医学部在过去的8年里。临床研究 的变化的混杂效应限制了心肌功能 前负荷和后负荷对心功能的影响。单个肌细胞的应用 在组织培养中的主要优势是允许评估 与载荷条件变化无关的收缩性能。 已经开发出一种利用自发殴打新生儿的系统 在培养皿中生长的大鼠心肌细胞，在一个时相下成像- 对比度显微镜，连接到电视监控系统，并提供数据 到一个分析系统，能够量化的幅度和速度 心肌细胞收缩。 使用该系统已经证明，败血症患者的血清 抑制心肌细胞收缩的数量和时间接近 与左心室射血分数降低的相关性研究 在活体内。因此，我们试图分离和描述这一点 来自人和败血症的一种或多种心肌抑制物质 犬标本；它似乎是一种具有相对分子质量的新分子 超过10K道尔顿。已知的败血症介质(即， 内毒素、白介素1和2以及肿瘤坏死因子)已被 用体外试验进行筛选。心肌抑制药的发生率 已对感染性休克的大型临床系列患者进行了活性检测 患者，并发现约40%。希望具体的 鉴定这些心肌抑制物质将直接导致 为脓毒症创造新的治疗方式。