The link between regional tidal stretch and lung injury during mechanical ventilation

Aim: This study aimed to assess the association between regional tidal volume (VT), 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 VT and FRC of the ventilated mice was determined from analysis of high-resolution four-dimensional 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 sVT 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 sVT 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 sVT.

Conclusion: These observations suggest that regional inflammatory responses to mechanical ventilation are primarily driven by tidal stretch.