Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (), sham-septic (), and healthy () animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy.

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高氧在腹腔内脓毒症临床前模型中引起的全身效应

补充氧气是脓毒症患者的支持性治疗，以平衡组织中的氧气输送和需求。然而，高氧可能会引起一些病理作用。我们试图在腹腔内脓毒症的临床前模型中评估与高氧相关的器官损伤及其与活性氧 (ROS) 产生的相关性。为此，通过盲肠结扎和穿刺 (CLP) 在雄性 Sprague-Dawley 大鼠中诱导败血症。我们将实验动物随机分配到三组：对照组（健康动物）、败血症（CLP）和假败血症（无 CLP 的手术干预）。在 CLP 后 18 小时，脓毒症（),假化粪池 (),和健康 ()将动物置于密封的有机玻璃笼内，随机分为四组，分别用 21%、40%、60% 或 100% 氧气连续治疗 24 小时。在实验结束时，我们评估了每只存活动物的血清细胞因子水平、器官损伤生物标志物、脑和肺组织的组织学检查以及 ROS 的产生。我们发现高氧浓度增加了 IL-6 和脓毒症动物器官损伤水平的生物标志物，尽管没有观察到相关的组织病理学肺或脑损伤。健康大鼠在高氧浓度下 IL-6 和天冬氨酸转氨酶增加。IL-6 水平而非 ROS 水平与器官损伤的标志物相关。在我们的研究中，在腹腔内脓毒症的临床相关模型中使用高氧浓度与炎症和器官损伤增强有关。这些发现与 ROS 释放到循环中无关。高氧会加剧败血症引起的炎症，而且它本身可能是有害的。我们的研究强调需要为氧疗制定更安全的阈值。