From the Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria (CH, JW, LS-G, EVT, KM, KUK); Department of Anaesthesia, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (JW); Department of Internal Medicine II, Medical University Vienna (CK, SS, JW); Ludwig-Boltzmann-Cluster for Cardiovascular Research (JW); Core Facilities, Medical University of Vienna, Vienna, Austria (JW).
Eur J Anaesthesiol. 2017 Mar;34(3):141-149. doi: 10.1097/EJA.0000000000000593.
Perioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs.
Our primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions.
In-vitro cell culture study.
Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014.
HUVECs were isolated from fresh umbilical cords.
HUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor.
Cell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways.
Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death-associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5' AMP-activated protein kinases 1/2.
Continuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury.
This in-vitro study was not registered in a database.
围手术期氧（O2）治疗可导致高氧血症。极度高氧血症可损伤心血管系统和远处器官。
我们的主要目的是检验这样一个假设，即暴露于中度高氧环境会导致人脐静脉内皮细胞（HUVEC）损伤，HUVEC 是一种在受控条件下研究血管内皮的模型。
体外细胞培养研究。
维也纳医科大学麻醉科、重症监护和疼痛管理科。研究时间为 2013 年 10 月初至 2014 年 7 月底。
HUVEC 从新鲜脐带中分离出来。
使用细胞培养生物反应器，将 HUVEC 暴露于持续高氧（40%O2）、周期性高氧/缺氧（40%/0%O2，平均 20%O2）、持续常氧（21%O2）和持续缺氧（0%O2）环境中。
在治疗 6、12、24 和 48 小时后，评估细胞生长、活力以及白细胞介素 6（IL-6）、白细胞介素 8（IL-8）和巨噬细胞移动抑制因子的释放情况。在治疗 60 分钟后进行磷酸激酶谱分析，以确定激活的细胞信号通路。
持续高氧和周期性高氧/缺氧均会抑制细胞生长，降低细胞活力，引发促炎反应，IL-6、IL-8 和移动抑制因子的释放证实了这一点，并诱导细胞凋亡和坏死。在持续高氧组中，炎症和细胞毒性反应最为强烈。磷酸激酶谱分析显示，不同的 O2 浓度会激活不同的细胞保护和细胞死亡相关激酶，包括丝裂原激活蛋白激酶、Src 激酶、p53、Akt、丝裂原和应激激活激酶、Lyn、Lck、p70S6、信号转导和转录激活因子 5b 和 6、糖原合酶激酶 3a/b 和 5' AMP 激活蛋白激酶 1/2。
持续的中度高氧和周期性中度高氧/缺氧诱导内皮炎症、凋亡和坏死。鉴于血管内皮的表面积较大，中等程度的 O2 水平可能会导致心血管炎症和损伤。
本体外研究未在数据库中注册。
