RESUMEN
Although oxygen (O2) is essential for aerobic life, it can also be an important source of cellular damage. Supra-physiological levels of O2 determine toxicity due to exacerbated reactive oxygen species (ROS) production, impairing the homeostatic balance of several cellular processes. Furthermore, injured cells activate inflammation cascades, amplifying the tissue damage. The lung is the first (but not the only) organ affected by this condition. Critically ill patients are often exposed to several insults, such as mechanical ventilation, infections, hypo-perfusion, systemic inflammation, and drug toxicity. In this scenario, it is not easy to dissect the effect of oxygen toxicity. Translational investigations with animal models are essential to explore injuring stimuli in controlled experimental conditions, and are milestones in understanding pathological mechanisms and developing therapeutic strategies. Animal models can resemble what happens in critical care or anesthesia patients under mechanical ventilation and hyperoxia, but are also critical to explore the effect of O2 on lung development and the role of hyperoxic damage on bronchopulmonary dysplasia. Here, we set out to review the hyperoxia effects on lung pathology, contributing to the field by describing and analyzing animal experimentation's main aspects and its implications on human lung diseases.
RESUMEN
BACKGROUND: Long-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism. METHODS: Twenty-four SD rats were randomly divided into 3 groups (n = 8/group): mechanical ventilated with normoxia group (MV group, FiO2 = 21%), with hyperoxia group (HMV group, FiO2 = 90%), or with hyperoxia + DFO group (HMV + DFO group, FiO2 = 90%). Mechanical ventilation under different oxygen concentrations was given for 4 h, and ECG was monitored. The HMV + DFO group received continuous intravenous infusion of DFO at 50 mgâ¢kg- 1â¢h- 1, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 and 4 h, respectively, and the PaO2/FiO2 ratio was calculated. After 4 h ventilation, the right anterior lobe of the lung and bronchoalveolar lavage fluid from the right lung was sampled for pathological and biochemical assays. RESULTS: PaO2 in the HMV and HMV + DFO groups were significantly higher, but the PaO2/FiO2 ratio were significantly lower than those of the MV group (all p < 0.01), while PaO2 and PaO2/FiO2 ratio between HMV + DFO and HMV groups did not differ significantly. The lung pathological scores and the wet-to-dry weight ratio (W/D) in the HMV and HMV + DFO groups were significantly higher than those of the MV group, but the lung pathological score and the W/D ratio were reduced by DFO (p < 0.05, HMV + DFO vs. HMV). Biochemically, HMV resulted in significant reductions in Surfactant protein C (SP-C), Surfactant protein D (SP-D), and Glutathion reductase (GR) levels and elevation of xanthine oxidase (XOD) in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO. CONCLUSIONS: Mechanical ventilation with hyperoxia for 4 h induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.