It is unclear how acid-induced lung injury alters the regional lung volume response to mechanical ventilation (MV) and how this impacts protein expression. Using a mouse model, we investigated the separate and combined effects of acid aspiration and MV on regional lung volumes and how these were associated with the proteome. Adult BALB/c mice were divided into four groups: intratracheal saline, intratracheal acid, saline/MV, or acid/MV. Specific tidal volume (sVt) and specific end-expiratory volume (sEEV) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography (4DCT) images. Lung tissue was dissected into 10 regions corresponding to the image segmentation for label-free quantitative proteomic analysis. Our data showed that acid aspiration significantly reduced sVt and caused further reductions in sVt and sEEV after 2 h of ventilation. Proteomic analysis revealed 42 dysregulated proteins in both Saline/MV and Acid/MV groups, and 37 differentially expressed proteins in the Acid/MV group. Mapping of the overlapping proteins showed significant enrichment of complement/coagulation cascades (CCC). Analysis of 37 unique proteins in the Acid/MV group identified six additional CCC proteins and seven downregulated proteins involved in the mitochondrial respiratory chain (MRC). Regional MRC protein levels were positively correlated with sEEV, while the CCC protein levels were negatively associated with sVt. Therefore, this study showed that tidal volume was associated with the expression of CCC proteins, while low end-expiratory lung volumes were associated with MRC protein expression, suggesting that tidal stretch and lung collapse activate different injury pathways.NEW & NOTEWORTHY This study provides novel insights into the regional response to mechanical ventilation in the setting of acid-induced lung injury and highlights the complex interaction between tidal stretch and low-end-expiratory lung volumes; both of which caused altered regulation of different injury pathways.
Keywords: acid aspiration; lung imaging; mechanical ventilation; ventilator-induced lung injury proteomics.