What is Ventilator-Induced Lung Injury (VILI)?

Ventilator-induced lung injury (VILI) is a form of lung damage that can occur as a complication of mechanical ventilation, particularly in individuals with pre-existing lung injury or acute respiratory distress syndrome (ARDS). Mechanical ventilation is a life-saving intervention used to support breathing in patients who are unable to adequately exchange oxygen and carbon dioxide on their own. However, if not carefully managed, mechanical ventilation can cause or exacerbate lung injury, leading to VILI.


Several mechanisms contribute to the development of VILI:


  • Barotrauma: Mechanical ventilation delivers air or oxygen to the lungs under pressure, which can cause overdistension of the alveoli (air sacs) beyond their physiological limits. This overdistension, known as barotrauma, can lead to alveolar rupture, resulting in air leaks into the surrounding tissues (pneumothorax) or the mediastinum (pneumomediastinum).


  • Volutrauma: Volutrauma refers to lung injury caused by excessive tidal volumes delivered during mechanical ventilation. High tidal volumes can stretch and damage the lung parenchyma, particularly in regions with heterogeneous lung compliance, leading to alveolar damage, inflammation, and impaired gas exchange.


  • Atelectrauma: Atelectrauma occurs when mechanical ventilation leads to repetitive opening and closing of collapsed alveoli, causing shear stress and inflammation in the lung tissue. This cyclic recruitment and derecruitment of alveoli can exacerbate lung injury and contribute to the release of pro-inflammatory mediators.


  • Oxygen Toxicity: High concentrations of oxygen delivered during mechanical ventilation can lead to oxidative stress and lung injury. Oxygen toxicity results from the generation of reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and DNA, leading to inflammation and tissue injury.


  • Biotrauma: Mechanical ventilation can trigger an inflammatory response in the lungs, known as biotrauma, characterized by the release of pro-inflammatory cytokines, chemokines, and other mediators. This inflammatory response can further exacerbate lung injury and contribute to systemic inflammation and organ dysfunction.


What is the relationship between VILI and oxidative stress?

The relationship between ventilator-induced lung injury (VILI) and oxidative stress involves complex interactions between mechanical ventilation-induced lung trauma and the generation of reactive oxygen species (ROS), leading to oxidative damage in the lung tissue. Several mechanisms contribute to the development of oxidative stress in VILI:


  • Mechanical Strain: Mechanical ventilation with high tidal volumes and pressures can cause excessive stretching and shearing forces on the lung tissue, leading to cellular damage and activation of inflammatory pathways. This mechanical strain induces the release of ROS from activated inflammatory cells, such as neutrophils and macrophages, as well as from damaged epithelial and endothelial cells.


  • Ischemia-Reperfusion Injury: Ventilation-induced changes in lung volume and pressure can disrupt blood flow to certain areas of the lung, resulting in ischemia and subsequent reperfusion injury upon lung expansion. Ischemia-reperfusion injury is a known trigger of oxidative stress, as the reintroduction of oxygen to previously ischemic tissue leads to the generation of ROS via mitochondrial dysfunction, xanthine oxidase activation, and NADPH oxidase activation.


  • Inflammatory Response: VILI triggers a robust inflammatory response characterized by the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. ROS are produced by inflammatory cells (such as neutrophils and macrophages) as part of their antimicrobial defense mechanisms. However, excessive ROS production can overwhelm endogenous antioxidant defenses and contribute to oxidative stress-induced lung injury.


  • Mitochondrial Dysfunction: Mechanical ventilation-induced lung injury can disrupt mitochondrial function in lung cells, leading to impaired cellular respiration and increased ROS production. Mitochondrial dysfunction can occur due to alterations in mitochondrial membrane permeability, disruption of electron transport chain complexes, and depletion of ATP levels, exacerbating oxidative stress and cellular damage in the lung tissue.


  • Antioxidant Depletion: Mechanical ventilation-induced oxidative stress can deplete endogenous antioxidant defenses in the lung tissue, exacerbating oxidative damage and inflammation. Antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase play crucial roles in neutralizing ROS and protecting cells from oxidative damage. However, excessive ROS production during VILI can overwhelm these antioxidant defenses, leading to oxidative stress-induced lung injury.


Overall, oxidative stress is a central mechanism underlying the pathogenesis of VILI, contributing to lung tissue damage, inflammation, and dysfunction.