Hyperoxia during one lung ventilation: inflammatory and oxidative responses

Abstract

Background: It is common practice during one lung ventilation (OLV) to use 100% oxygen, although this may cause hyperoxia- and oxidative stress-related lung injury. We hypothesized that lower oxygen (FiO(2) ) during OLV will result in less inflammatory and oxidative lung injury and improved lung function.

Methods: Twenty pigs (8.88 ± 0.84 kg; 38 ± 4.6 days) were assigned to either the hyperoxia group (n = 10; FiO(2) = 100%) or the normoxia group (n = 10; FiO(2) < 50%). Both groups were subjected to 3 hr of OLV. Blood samples were tested for pro-inflammatory cytokines and lung tissue was tested for these cytokines and oxidative biomarkers.

Results: There were no differences between groups for partial pressure of CO(2) , tidal volume, end-tidal CO(2) , plasma cytokines, or respiratory compliance. Total respiratory resistance was greater in the hyperoxia group (P = 0.02). There were higher levels of TNF-α, IL-1β, and IL-6 in the lung homogenates of the hyperoxia group than in the normoxia group (P ≤ 0.01, 0.001, and 0.001, respectively). Myeloperoxidase and protein carbonyls (PC) were higher (P = 0.03 and P = 0.01, respectively) and superoxide dismutase (SOD) was lower in the lung homogenates of the hyperoxia group (P ≤ 0.001).

Conclusion: Higher myeloperoxidase, PC, and cytokine levels, and lower SOD availability indicate a greater degree of injury in the lungs of the hyperoxia animals, possibly from using 100% oxygen. In this translational study using a pig model, FiO(2) ≤ 50% during OLV reduced hyperoxic injury and improved function in the lungs.

Fig. 1

Partial pressure of oxygen (PaO₂) over time. This figure shows the hyperoxia group with a higher mean PaO₂ than the normoxia group from the baseline, through one lung ventilation, to the endpoint measurement (P ≤ 0.02 by repeated measures ANOVA). This difference is expected, since the FiO₂ for the hyperoxia group was held at 100% for the duration of the experiment, while the FiO₂ for the normoxia group was maintained at or below 50%. There is also greater variability in dispersion of data points for PaO₂ in the hyperoxia group for each time point. ^*Significance at the P ≤ 0.001 level.

Fig. 2

Pro-inflammatory cytokines in lung tissue. Levels of pro-inflammatory cytokines in lung-tissue homogenates from the collapsed and ventilated lungs of animals in the hyperoxia group and the normoxia group. There was an overall group difference observed for tumor necrosis factor (TNF)- α (A), interleukin (IL)-1β (B), and IL-6 (C) at P < 0.01, 0.001, and 0.001, respectively, independent of whether the lung was collapsed or ventilated. No difference was seen between groups for IL-8 (D). Levels of these markers were higher in the lungs of animals in the hyperoxia group, thus indicating a greater degree of inflammation from exposure to a FiO₂ of 1. Note that to improve clarity for the IL-1β graph, the split Y-axis excludes the 20–1000 range.

Fig. 3

Oxidative injury markers in lung tissue. Levels of oxidative injury markers in lung-tissue homogenates from the collapsed and ventilated lungs of animals in the hyperoxia group and the normoxia group. Overall group differences existed for myeloperoxidase (MPO) (A; P = 0.03), protein carbonyls (PC) (B; P ≤ 0.02) and superoxide dismutase (SOD) (C; P ≤ 0.001) by two-way ANOVA, independent of whether the lung was collapsed or ventilated. The hyperoxia group shows higher levels of MPO and PCs, suggesting a greater amount of reactive oxygen species in this group. The abundance of reactive oxygen species in the lungs of hyperoxia group animals may have resulted in a depletion of available SOD, explaining why the hyperoxia group had lower levels of SOD compared to the normoxia group.

Fig. 4

Representative histology. Hematoxylin- and eosin-stained base nondependent lung tissue harvested following endpoint measures of one lung ventilation (OLV) experiment and viewed at 10× magnification. In both groups, the collapsed lung shows greater alveolar wall thickening and polymorphonuclear infiltrates when compared with the ventilated lung. In the hyperoxia group, greater numbers of red blood cells are visible in the alveolar lumen compared to the normoxia group, which may suggest greater pulmonary permeability due to oxidative injury.