Department of Emergency, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning, China.
Department of Emergency, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou City, Henan, China.
Shock. 2023 Nov 1;60(5):664-670. doi: 10.1097/SHK.0000000000002225. Epub 2023 Sep 5.
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.
心脏骤停（CA）后的缺血再灌注会激活肽基精氨酸脱亚氨酶和瓜氨酸化组蛋白 H3（CitH3），导致中性粒细胞胞外诱捕网（NETs）的形成。本研究试图确定 CA 后患者 NET 成分的变化，并分析 NETs 与 28 天全因死亡率的关系。
本研究纳入了 95 例自主循环恢复（ROSC）后的 CA 患者。根据 28 天的生存状况，将他们分为幸存者组（n=32）和非幸存者组（n=63）。对照组包括 20 名健康个体。患者在 ROSC 后第 1、3 和 7 天以及对照组个体入组时采集血样。采用荧光标记法测定血清细胞游离 DNA（cfDNA）水平，采用酶联免疫吸附试验测定血清 NET 成分（包括 CitH3、髓过氧化物酶、中性粒细胞弹性蛋白酶和核小体）浓度。
与对照组相比，ROS 后 1 周患者的血清 NET 成分显著升高（均 P<0.05）。非幸存者组明显高于幸存者组（均 P<0.05）。Spearman 相关性分析显示，这些成分与急性生理学和慢性健康评估 II 评分呈正相关（均 P<0.05）。二元逻辑回归分析表明，ROS 后第 1、3 天的血清 cfDNA、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 ROS 后第 1 天的受试者工作特征曲线下面积最大（分别为 0.876、0.862 和 0.861）。
ROS 后血清 cfDNA、CitH3、髓过氧化物酶、中性粒细胞弹性蛋白酶和核小体水平升高与 ROSC 后疾病严重程度呈正相关。然而，只有 ROS 后第 1 天的血清 CitH3、cfDNA 和核小体对 28 天全因死亡率具有良好的预测价值。
