Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Toxins (Basel). 2017 Dec 6;9(12):394. doi: 10.3390/toxins9120394.
Shock with infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET respectively) both cause shock and likely contribute to the high lethality rate with . Selective inhibition of the toxins is protective in infection models, and administration of either toxin alone in animals produces hypotension with accompanying organ injury and lethality. Shock during infection is typically due to one of two mechanisms: (i) intravascular volume depletion related to disruption of endothelial barrier function; and (ii) extravasation of fluid and/or maladaptive dilation of peripheral resistance arteries. Although some data suggests that LT can produce myocardial dysfunction, growing evidence demonstrates that it may also interfere with endothelial integrity thereby contributing to the extravasation of fluid that helps characterize severe infection. Edema toxin, on the other hand, while known to produce localized tissue edema when injected subcutaneously, has potent vascular relaxant effects that could lead to pathologic arterial dilation. This review will examine recent data supporting a role for these two pathophysiologic mechanisms underlying the shock LT and ET produce. Further research and a better understanding of these mechanisms may lead to improved management of in patients.
感染性休克对常规心血管支持具有较强的抵抗力，其死亡率似乎高于常见的细菌性病原体。与许多缺乏直接抑制血流动力学功能的外毒素的细菌不同，致死毒素（LT）和水肿毒素（ET）均可引起休克，并可能导致感染性休克的高致死率。毒素的选择性抑制在感染模型中具有保护作用，单独给予两种毒素中的任何一种都会导致低血压，伴随器官损伤和致死率。感染期间的休克通常归因于以下两种机制之一：（i）内皮屏障功能破坏导致的血管内容积减少；和（ii）液体外渗和/或外周阻力动脉的适应性扩张。尽管一些数据表明 LT 可能导致心肌功能障碍，但越来越多的证据表明，它还可能干扰内皮完整性，从而有助于导致特征性严重感染的液体外渗。另一方面，水肿毒素虽然已知在皮下注射时会产生局部组织水肿，但具有很强的血管舒张作用，可能导致病理性动脉扩张。这篇综述将探讨支持 LT 和 ET 引起休克的这两种病理生理机制的最新数据。进一步的研究和对这些机制的更好理解可能会导致感染患者管理的改善。
