A high fraction of inspired oxygen does not mitigate atelectasis-induced lung tissue hypoxia or injury in experimental acute respiratory distress syndrome

Abstract

Background Although alveolar hyperoxia exacerbates lung injury, clinical studies have failed to demonstrate the beneficial effects of lowering the fraction of inspired oxygen (F_IO₂) in patients with acute respiratory distress syndrome (ARDS). Atelectasis, which is commonly observed in ARDS, not only leads to hypoxemia but also contributes to lung injury through hypoxia-induced alveolar tissue inflammation. Therefore, it is possible that excessively low F_IO₂ may enhance hypoxia-induced inflammation in atelectasis, and raising F_IO₂ to an appropriate level may be a reasonable strategy for its mitigation. In this study, we investigated the effects of different F_IO₂ levels on alveolar tissue hypoxia and injury in a mechanically ventilated rat model of experimental ARDS with atelectasis. Methods Rats were intratracheally injected with lipopolysaccharide (LPS) to establish an ARDS model. They were allocated to the low, moderate, and high F_IO₂ groups with F_IO₂ of 21, 60, and 100%, respectively, a day after LPS injection. All groups were mechanically ventilated with an 8 mL/kg tidal volume and zero end-expiratory pressure to induce dorsal atelectatic regions. Arterial blood gas analysis was performed every 2 h. After six hours of mechanical ventilation, the rats were euthanized, and blood, bronchoalveolar lavage fluid, and lung tissues were collected and analyzed. Another set of animals was used for pimonidazole staining of the lung tissues to detect the hypoxic region. Results Lung mechanics, ratios of partial pressure of arterial oxygen (P_aO₂) to F_IO₂, and partial pressure of arterial carbon dioxide were not significantly different among the three groups, although PaO2 changed with F_IO₂. The dorsal lung tissues were positively stained with pimonidazole regardless of F_IO₂, and the HIF-1α concentrations were not significantly different among the three groups, indicating that raising F_IO₂ could not rescue alveolar tissue hypoxia. Moreover, changes in F_IO₂ did not significantly affect lung injury or inflammation. In contrast, hypoxemia observed in the low F_IO₂ group caused injury to organs other than the lungs. Conclusions Raising F_IO₂ levels did not attenuate tissue hypoxia, inflammation, or injury in the atelectatic lung region in experimental ARDS. Our results indicate that raising F_IO₂ levels to attenuate atelectasis-induced lung injury cannot be rationalized.