University Hospital Services, University of Alabama at Birmingham (UAB), Birmingham, AL 35294, USA.
Lab Invest. 2010 Jan;90(1):128-39. doi: 10.1038/labinvest.2009.119. Epub 2009 Nov 9.
Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a 'cytokine storm', leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-alpha and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have an important pathophysiological role in ECMO-related SIRS.
体外膜肺氧合（ECMO）是一种用于严重心肺衰竭新生儿和幼儿的救生支持系统。尽管 ECMO 降低了这些危重病患者的死亡率，但几乎所有接受 ECMO 治疗的患者都会出现全身性炎症反应综合征（SIRS），其特征是“细胞因子风暴”、白细胞活化和多器官功能障碍。我们使用新生猪 ECMO 模型来研究 ECMO 期间炎症细胞因子的血浆浓度升高是否反映了这些介质在炎症组织中的从头合成，因此可以用于评估 ECMO 相关 SIRS 的严重程度。先前健康的小猪（3 周龄）接受静脉动脉 ECMO 长达 8 小时。通过组织病理学分析、中性粒细胞活化（流式细胞术）、血浆细胞因子浓度（酶免疫测定）和炎症基因的组织表达（PCR/免疫印迹）评估 SIRS。通过测量血浆胰蛋白酶活性来研究肥大细胞脱颗粒。新生猪 ECMO 与人类新生儿中所见的全身性炎症变化相似。肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）浓度在 ECMO 的头 2 小时内迅速升高，比这些细胞因子的组织表达更快。ECMO 与血浆肥大细胞胰蛋白酶活性增加有关，表明 ECMO 期间炎症细胞因子的血浆浓度升高可能是由于肥大细胞脱颗粒和相关释放储存在肥大细胞中的预先形成的细胞因子。ECMO 期间，TNF-α和 IL-8 浓度在血浆中比在外周组织中升高更快，表明 ECMO 启动后立即升高的这些细胞因子的血浆水平可能不反映这些细胞因子组织合成的增加。炎症细胞因子如黏膜肥大细胞中预先形成的细胞储存的动员可能在 ECMO 相关 SIRS 中具有重要的病理生理作用。
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