Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

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.

Effect of low-to-moderate hyperoxia on lung injury in preclinical animal models: a systematic review and meta-analysis

“…S1) [ 32 – 55 ]. Ten studies compared the effects of FiO 2 s ≤ 0.60/ > 0.21 to FiO 2 = 0.21 in animals challenged with an infectious ( n = 6 studies) or noninfectious ( n = 4) inflammatory challenge [ 32 – 34 , 37 , 38 , 43 , 45 , 49 , 51 , 52 ] and 14 studies compared these FiO 2 s alone [ 35 , 36 , 39 – 42 , 44 , 46 – 48 , 50 , 53 – 55 ]. The two groups of studies were examined separately.…”

“…The present literature search retrieved more than 600 animal studies investigating only FiO 2 > 0.60. By contrast, despite ongoing questions regarding the potential risks of lower FiO 2 s in critically ill patients, this search retrieved only 10 studies examining the impact of FiO 2 ≤ 0.60 and > 0.21 (FiO 2 ≤ 0.60/ > 0.21) on survival or lung injury in animals administered an infectious or noninfectious inflammatory challenge [ 32 – 34 , 37 , 38 , 43 , 45 , 49 , 51 , 52 ] and 14 studies examining these FiO 2 s alone [ 35 , 36 , 39 – 42 , 44 , 46 – 48 , 50 , 53 – 55 ]. The differing study designs and parameters measured and sometimes inconsistent effects across the limited numbers of studies examining similar or related parameters provide no firm conclusion as to the overall effects of FiO 2 ≤ 0.60/ > 0.21 in either group of studies.…”

Effects of Normoxia, Hyperoxia, and Mild Hypoxia on Macro-Hemodynamics and the Skeletal Muscle Microcirculation in Anesthetised Rats

“…Third, we observed a similar reduction in Hb levels in all groups, which was probably due to hemodilution and repeated blood sampling: this may have influenced the macro-hemodynamic and microvascular responses observed by contributing to changes in CaO 2 and blood viscosity. Fourth, we did not measure markers of oxidative stress ( 37 ) or inflammation ( 38 ): this may have helped to understand the pathophysiological basis of cardiovascular changes induced by hyperoxia. Moreover, we did not measure variations in NO levels and could not demonstrate the role of NO in microvascular perturbations induced by hypoxia/hyperoxia.…”

Hyperoxia in the ICU and what has changed in 100 years in the tactics of using oxygen in medicine: a review

“…Гипероксия может усугубить воспаление, вызванное сепсисом, и сама по себе может быть пагубной. L. Isabel Garcia-Laorden et al отмечают необходимость разработки более безопасных пороговых значений для кислородной терапии [45].…”