Mechanical ventilation (MV) causes oxidative stress that is responsible for adverse consequences on organs. In a situation of MV, the excessive pressure impairs the function of the mitochondrial respiratory chain leading to oxidative and nitrosative stress (Kavazis, 2009; Hafner et al., 2014). MV is commonly associated with hyperoxia where an excess of oxygen is provided. In such a case an oxidative stress can be induced when the oxygen pressure in the alveolar exceeds that of the normal breathing conditions because the biological system is not able to readily detoxify the environment from components such as reactive oxygen species (ROS) ( Kala et al., 2015). The oxidative stress is also initiated by perturbations in the normal redox state of the cells that can trigger the production of peroxidases and free radicals responsible for severe damage to many components of the cell such as proteins lipid and DNA injury (Powers et al., 2009; Tobin et al., 2010). Oxidative stress can cause damage to organs by stimulating of protein-degradation pathways (Whidden et al., 2010). During an MV, the inspired oxygen fraction (FiO2) is an MV parameter that can help improve tissue oxygenation, but can also lead to detrimental effects of hypoxia or hyperoxia if not adjusted adequately (Mash et al., 2011; Filho et al., 2012). This can cause an imbalance between the amount of oxygen provided and the amount needed by the system as well as the amount that the system can metabolise. The imbalance becomes thereby a triggering factor for oxidative stress. Filho et al. (2012) conducted a study to assess the correlation between oxidative stress in the plasma and erythrocytes and found that individuals undergoing invasive MV can develop redox state modifications accompanied with an augmentation of thiobarbituric acid reacting substances (TBARS) and reduced antioxidant enzymes. Moreover, the increased in TBARS observed under oxidative stress as a result of MV, could be related to endothelial dysfunction caused by an enhanced release of oxygen-derived free radicals and ROS, such as hydrogen peroxide responsible for both pulmonary and systemic injuries (Filho et al., 2012; Kala et al., 2015). Respiratory muscle contractions, resulting from invasive MV, facilitate transient ischemia, whereas relaxation triggers reperfusion. The latter process characterizes the oxygen paradox where an absence of oxygen associated with a subsequent reperfusion triggers an increased release of ROS and an unbalanced condition. MV-induced oxidative stress has been shown to be involved in the production of Ischemia-modified albumin (IMA, a variant of a human serum albumin) in neonates receiving MV(Dursun et al., 2016). The occurrence of the latter components is reported to be related to ROS.
MV is commonly associated with an increase production of ROS, which induces oxidative stress (Kavazis, 2009). The increased amount of ROS is related to various factors. It is well known that MV can damage alveolar and elements of the parenchyma, causing a pneumothorax (Tobin et al., 2010). When the alveolar capillary endothelium is activated, it exhibits an increased adhesiveness responsible for an accumulation of various cells such as neutrophils which are sources of ROS. Protective antioxidant defences can become overwhelmed with ROS leading to oxidative stress (Kala et al., 2015). For the metabolic activities of the cell such the one for glucose, oxygen is required for the cellular respiration. In the mitochondria, most of the oxygen is used for the production of adenosine triphosphate (ATP) and the process generate oxidizing free radical and ROS especially when a toxic level of O2 is present (kala et al., 2015). ROS and free radicals are produced by the reduction of molecular oxygen into water (Bhattacharya, 2014). Also, a damage of the alveolar capillary triggers an impaired gas exchange and pulmonary edema. In such as a case, ROS induces the production of chemoattractants, and cytokines by the pulmonary cells. The later process activates the mobilization and accumulation of macrophage and monocyte in the lungs, leading to additional ROS.
When not well adjusted, MV can cause hypoxia that can lead to adverse consequences such as cell modifications and amplified anaerobic metabolism (Filho et al., 2012). In a situation of hypoxia, a nitrosative stress can occur. This is characterised by the production an amount of reactive nitrogen species that the body the cell can neutralise (Wagner et al., 2015). Conducting experience on mice that have undergone MV after exposure to cigarette smoking, the latter authors observed an increase in nitrosative stress and explained that this was related to the fact that under normal hypoxia there is an excessive production of nitrite oxide (NO) that inhibit the mitochondrial respiration. This occurs as a result of a reduction in the accumulation of the Hypoxia-inducible factor 1-alpha (HIF-1α ) cause by an NO-mediated feedback associated with an expression of prolyl-hydroxylases (PHD) and/or O2-redistribution to PHD (Berchner-Pfannenschmid, 2010). Generally, under standard oxygen conditions the release of hyper-inflammation-induced NO cause impairment of the HIF-1α degradation because PHD are inhibited.
References
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