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Abstract
Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure–volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure–volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.
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1 University of California, Department of Mechanical Engineering, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582)
2 University of California, Division of Biomedical Sciences, Riverside School of Medicine, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); University of California Riverside, Environmental Toxicology Graduate Program, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582)
3 University of California, Division of Biomedical Sciences, Riverside School of Medicine, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582)
4 University of California, Division of Biomedical Sciences, Riverside School of Medicine, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); University of California Riverside, Environmental Toxicology Graduate Program, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); University of California, BREATHE Center, School of Medicine, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); Colorado State University, Department of Environmental and Radiological Health Sciences, Fort Collins, USA (GRID:grid.47894.36) (ISNI:0000 0004 1936 8083)
5 University of California, Department of Mechanical Engineering, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); University of California, BREATHE Center, School of Medicine, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582); University of California, Department of Bioengineering, Riverside, USA (GRID:grid.266097.c) (ISNI:0000 0001 2222 1582)