Alveolar Cell Wounding by Deforming Stress in the Lung

Richard A. Oeckler, Rolf D. Hubmayr

Abstract

Ventilator-induced lung injury (VILI) is recognized as a hospital-acquired condition and significant source of morbidity and mortality in patients exposed to mechanical ventilation at injurious settings. Wounded lung cells are important transducers of injurious stress, and through the process of mechanotransduction the physical and chemical signals emitted from these cells lead to the deleterious sequelae of acute lung injury. Low tidal volume (VT) ventilation strategies have improved outcomes by minimizing deforming stress and associated lung injury, yet the mechanisms surrounding the inciting mechanotransduction event, the mechanical wounding and disruption of the alveolar epithelium, remain poorly characterized.

Regional variation in lung mechanics due to preexisting disease, acute pathological processes, prestress of the parenchyma by gravity, and the selection of ventilator settings, influence the topographical distribution of VT and deformation experienced by constituent lung cells. In this short review we explore the mechanical effects of VT on deformation and stress experienced by airway constituent cells, and outline two distinct mechanisms of alveolar cell injury by deforming stress: Overdistension and interfacial injury. The general cytoskeletal polymerization state and associated load-bearing elements (actin anchoring proteins, cell-cell junctions, and focal adhesions) contribute biophysical determinants of injury common to both mechanisms and ought be explored for potential therapeutic applications. Nonetheless these mechanisms are unique and evidence suggests that cytoprotective interventions targeting interfacial injury are not likely to protect against overdistension or vice versa. Such complexity may account for some of the variable success with ‘ lung protective strategies’ at the bedside.

Keywords: ALI, alveolar cell, lung injury, mechanotransduction, overdistension, stretch, VILI

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