STUDIES OF SEPSIS UTILIZING SPONTANEOUSLY BEATING MYOCYTES IN TISSUE CULTURE

脓毒症时的心肌功能障碍一直是近年来研究的热点。 在过去的8年里，重症医学科。 临床研究 心肌功能的变化受到以下因素的混杂效应的限制： 前负荷和后负荷对心室功能的影响 使用单个肌细胞 在组织培养中的主要优点是允许评估 收缩性独立于负载条件的变化。 一个系统已经开发出来，利用自发跳动的新生儿 在培养皿中生长的大鼠肌细胞，在相- 对比显微镜，连接到电视监控系统，数据反馈 涉及一种能够量化 肌细胞收缩 使用该系统，已经证明来自脓毒症患者的血清 抑制心肌细胞收缩，在关闭定量和时间 与左心室射血分数下降相关 in vivo. 因此，我们试图分离和描述这一点， 人和败血症患者的心肌炎物质（或多种物质） 犬标本;它似乎是一种新的分子，分子量 分子量大于一万道尔顿。 已知的脓毒症介质（即， 内毒素、白细胞介素1和2以及肿瘤坏死因子）已经被 使用体外测定筛选。 心肌梗死的发生率 在大量的败血性休克的临床系列中， 患者，并发现约40%。 希望具体 这些心肌炎物质鉴定将直接导致 创造新的败血症治疗方法。

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.