Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest
Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest
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DOI：
10.1016/j.resuscitation.2016.08.006
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发表时间：
2016-10-01
期刊：
影响因子：
6.5
通讯作者：
Kjaergaard, Jesper
中科院分区：
文献类型：
--
作者：
Bro-Jeppesen, John;Johansson, Par I.;Kjaergaard, Jesper
背景：心脏骤停综合征（PCAS）以全身缺血引发全身炎症和内皮细胞损伤为特征。本研究探讨了全身炎症、内皮损伤和PCAS严重程度之间的关系，以及院外心脏骤停（OHCA）后内皮损伤与预后之间的关系。方法：在这项事后研究中，我们分析了163名昏迷患者，他们被纳入目标温度管理（TTM）试验，随机分配到33℃或36℃的TTM治疗24小时。内皮生物标志物（syndecan-1、血栓调节素、硒选择素、sVE-cadherin）和炎症生物标志物白介素-6 （IL-6）在入院（基线）和OHCA后24、48和72小时进行测量。采用序贯器官衰竭评分评价PCAS的严重程度。30 d死亡率采用Cox回归分析。结果：通过线性回归，基线IL-6水平（两倍）与OHCA后24h的糖萼损伤(syndecan-1 （10.3 ng/ml (p = 0.01)）、内皮活化(se -选择素（2.0 ng/ml (p = 0.03)）和内皮损伤（血栓调节素0.7 ng/ml (p = 0.0005)）独立相关。根据基线IL-6调整后，从基线到48小时（1.7 (0.9-2.4),p < 0.0001）和72小时（1.5 (0.6-2.3),p < 0.0007）血栓调节蛋白的两倍增加与PCAS的严重程度比IL-6更密切相关。syndecan-1、血栓调节素和sVE-cadherin的水平不受目标温度水平的影响，但se -选择素的水平在36℃组（-55 ng/ml (95%CI: -53至-58 ng/ml), p = 0.005）显著低于33℃组。在单变量分析中，24小时（HR = 2.1 (1.3-3.3), p = 0.001）和48小时（HR = 1.75 (1.0-2.8), p = 0.02）高水平的血栓调节素与30天死亡率增加相关，但在多变量分析中无相关。结论：在OHCA与TTM治疗后的昏迷幸存者中，全身炎症与内皮活化和内皮损伤有关。持续的内皮损伤与PCAS的严重程度独立相关，并根据全身炎症水平进行调整。与OHCA后的33℃相比，36℃时的TTM与内皮活化降低有关，但与内皮损伤无关。2016爱思唯尔爱尔兰有限公司版权所有。
Background: Post-cardiac arrest syndrome (PCAS) is characterized by whole-body ischemia triggering systemic inflammation and damage of the endothelium. This study investigated the relationship between systemic inflammation, endothelial damage and severity of PCAS and the association between endothelial damage and outcome after out-of-hospital cardiac arrest (OHCA).Methods: In this post hoc study, we analyzed 163 comatose patients included at a single center in the target temperature management (TTM) trial, randomly assigned to TTM at 33 degrees C or 36 degrees C for 24 h. Endothelial biomarkers (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin) and the inflammatory biomarker interleukin-6 (IL-6) were measured at admission (baseline) and 24, 48 and 72 h after OHCA. Severity of PCAS was assessed by Sequential Organ Failure Assessment score. Mortality at 30-days was evaluated by Cox regression analysis.Results: By linear regression, baseline IL-6 levels (two-fold) was independently associated with glycocalyx damage (syndecan-1 (10.3 ng/ml (p = 0.01))), endothelial activation (sE-selectin (2.0 ng/ml (p = 0.03))) and endothelial damage (thrombomodulin 0.7 ng/ml (p = 0.0005)) at 24h after OHCA. Adjusted for baseline IL-6, a two-fold increase in thrombomodulin from baseline to 48 h (1.7 (0.9-2.4), p < 0.0001) and 72 h (1.5 (0.6-2.3), p < 0.0007) was more closely associated with severity of PCAS than IL-6. Levels of syndecan-1, thrombomodulin and sVE-cadherin was not influenced by level of target temperature but levels of sE-selectin was significantly lower in the 36 degrees C group (-55 ng/ml (95%CI: -53 to -58 ng/ml), p = 0.005) compared to the 33 degrees C group. High levels of thrombomodulin at 24 h (HR = 2.1 (1.3-3.3), p = 0.001) and 48 h (HR = 1.75 (1.0-2.8), p = 0.02) were associated with increased 30-day mortality in univariate analysis, but not in multivariable analyses.Conclusion: In comatose survivors after OHCA treated with TTM, systemic inflammation was associated with endothelial activation and endothelial damage. Sustained endothelial damage was independently associated with severity of PCAS, adjusted for level of systemic inflammation. TTM at 36 degrees C compared to 33 degrees C after OHCA was associated with lower endothelial activation, but not endothelial damage. (C) 2016 Elsevier Ireland Ltd. All rights reserved.