Abstract:
Background: Ischemia-reperfusion after cardiac arrest (CA) activates peptidyl arginine deiminase and citrullinated histone H3 (CitH3), which leads to the formation of neutrophil extracellular traps (NETs). This study attempted to determine the alterations in NET components in post-CA patients as well as analyze the association of NETs with 28-day all-cause mortality. Methods : In this study, 95 patients with restoration of spontaneous circulation (ROSC) after CA were included. They were categorized into the survivor group (n = 32) and the nonsurvivor group (n = 63) according to their 28-day survival statuses. The control group comprised 20 healthy individuals. The blood samples were collected from the patients on days 1, 3, and 7 after ROSC and from the control subjects at the time of enrollment. The serum cell-free DNA (cfDNA) level was determined using the fluorescent labeling method, and the serum concentrations of NET components, including CitH3, myeloperoxidase, neutrophil elastase, and nucleosomes, were estimated using the enzyme-linked immunosorbent assay. Results : Compared with the control group, the serum NET components were significantly increased in the patients 1 week after ROSC (all P < 0.05). These components were significantly higher in the nonsurvivor group than in the survivor group (all P < 0.05). Spearman correlational analysis revealed that the components were positively correlated with Acute Physiology and Chronic Health Evaluation II scores (both P < 0.05). Binary logistic regression analysis indicated that serum cfDNA, CitH3, and nucleosomes on days 1 and 3 after ROSC were independent predictors of 28-day all-cause mortality. Furthermore, these parameters on day 1 after ROSC had the biggest areas under the receiver operating characteristic curves (0.876, 0.862, and 0.861, respectively). Conclusions: Elevated serum levels of cfDNA, CitH3, myeloperoxidase, neutrophil elastase, and nucleosomes were positively correlated with disease severity after ROSC. However, only serum CitH3, cfDNA, and nucleosomes on day 1 after ROSC showed a good predictive value for 28-day all-cause mortality.
摘要:
背景:心脏骤停后缺血再灌注激活肽基精氨酸脱亚胺酶和瓜氨酸组蛋白H3(CitH3),这导致中性粒细胞胞外陷阱(NET)的形成。这项研究试图确定心脏骤停后患者NET成分的变化,并分析NETs与28天全因死亡率的相关性。
方法:在本研究中,包括95例心脏骤停后恢复自主循环(ROSC)的患者。根据其28天的生存状况,将其分为幸存者组(n=32)和非幸存者组(n=63)。对照组包括20名健康个体。在ROSC后第1、3和7天从患者和在登记时从对照受试者收集血液样品。采用荧光标记法测定血清无细胞DNA(cfDNA)水平,以及NETs成分的血清浓度,包括CitH3,髓过氧化物酶(MPO),中性粒细胞弹性蛋白酶(NE),和核小体,使用酶联免疫吸附测定进行估计。
结果:与对照组相比,ROSC术后1周患者血清NET成分明显升高(P均<0.05)。非幸存者组的这些成分均明显高于幸存者组(均P<0.05)。Spearman相关分析显示各组分与APACHEⅡ评分呈正相关(均P<0.05)。二元logistic回归分析表明,血清cfDNA,ROSC后第1天和第3天的CitH3和核小体是28天全因死亡率的独立预测因子。此外,这些参数在ROSC后第1天的ROC曲线下面积最大(分别为0.876,0.862和0.861).
结论:血清cfDNA水平升高,CitH3,MPO,NE,核小体与ROSC术后疾病严重程度呈正相关。然而,只有血清CitH3,cfDNA,ROSC后第1天的核小体对28天全因死亡率具有良好的预测价值。