Abstract
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 (n = 39), sham-septic (n = 16), and healthy (n = 24) 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.
Highlights
Sepsis is a life-threatening organ dysfunction syndrome that results from a deregulated host response to infection [1]
Serum levels of tumor necrosis factor-α (TNF-α) were under the detection limit, while IL-10 levels did not change among oxygen groups
We found a moderated correlation between reactive oxygen species (ROS) and IL-6 in septic animals exposed to 100% O2 (r = 0:731, P = 0:040), but not for other O2 concentrations, nor when comparisons were made independent of O2
Summary
Sepsis is a life-threatening organ dysfunction syndrome that results from a deregulated host response to infection [1]. Sepsis remains a main cause of hospital mortality, and it is associated with poor long-term outcomes after hospital discharge [1,2,3]. Organ system failures defining sepsis include circulatory, renal, pulmonary, hepatic, hematologic, and central nervous systems [4]. Multiple organ dysfunction (MOD) is more common than single organ failure during sepsis. Sepsis is the most common cause of acute respiratory failure in critically ill patients, and the respiratory system dysfunction is mainly characterized by hypoxemia
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