The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation

Abstract

Aim: This study aimed to assess the association between regional tidal volume (V T), regional functional residual capacity (FRC) and the expression of genes linked with ventilator-induced lung injury. Methods: Two groups of BALB/c mice (n = 8 per group) were ventilated for 2 h using a protective or injurious ventilation strategy, with free-breathing mice as controls. Regional V T and FRC of the ventilated mice was determined from analysis of high-resolution fourdimensional computed tomography (4D-CT) images, taken at baseline and after 2 h of ventilation and corrected for the volume of the region (i.e. specific [s]Vt and specific [s]FRC). RNA levels of 21 genes in ten different lung regions were quantified using qPCR array. Results: sFRC at baseline varied regionally, independent of ventilation strategy, whereas sV T varied regionally depending on ventilation strategy. The expression of IL-6 (P = 0.04), Ccl2 (P < 0.01) and Ang 2 (P < 0.05) were associated with sV T but not sFRC. The expression of seven other genes varied regionally (IL-1β and RAGE) or depended on ventilation strategy (Nfe2l2, c-fos and Wnt1) or both (TNF-α and CxCl2), but were not associated with regional sFRC or sV T. Conclusion: These observations suggest that regional inflammatory responses to mechanical ventilation are primarily driven by tidal stretch.

Mechanical stretch and LPS affect the proliferation, extracellular matrix remodeling and viscoelasticity of lung fibroblasts

“…The lung is a mechanical organ. Mechanical ventilation causes repeated stress on the lung tissue and exerts mechanical stretch effects on alveolar epithelial cells, lung fibroblasts and pulmonary macrophages (14). In the pathological state of ARDS, different mechanical stretch modes and amplitudes have different molecular biological and cytological effects on lung tissue cells, affecting gene expression and metabolism of cells.…”

The proteomic response is linked to regional lung volumes in ventilator-induced lung injury

“…An understanding of these heterogeneities will help clarify how mechanical forces during MV amplify lung injury and thus inform the design of optimised ventilation strategies to minimize such injury. Recently, in healthy mouse lungs, we showed that the magnitude of regional tidal stretch in response to mechanical ventilation was linked to the regional expression of inflammatory genes [7]. In line with this, studies in sheep have shown that regional tidal strain in response to MV alters markers of metabolism [8].…”

“…Adult female BALB/c mice were anesthetized, tracheostomized, and mounted upright in a custom-built holder on a rotating stage as described previously [7]. The animals were randomly assigned to four groups (n = 7 per group).…”

“…As described previously [7,9], 4DCT images were captured using a liquid-metal-jet X-ray source coupled with a high-speed detector [15]. A 3D velocimetry technique [16] was applied to the dynamic images to calculate regional tidal volume (Vt) while Hounsfield Units were used to determine the aeration fraction at end expiration to obtain end-expiratory volume (EEV).…”

“…Acid aspiration is a well-known cause of the acute respiratory distress syndrome (ARDS) which leads to respiratory failure and a requirement for mechanical ventilation [14]. The purpose of this study was to evaluate the effect of MV in the setting of acid-induced lung injury on the lung volume response, using a four dimensional computed tomography (4DCT) lung imaging technology [7,9], and to link this with the regional proteomic response. We hypothesised that pre-existing lung injury would alter the lung volume response to MV and that this would result in the dysregulation of multiple molecular pathways in a lung region-specific manner.…”