Extracellular matrix remodeling modifies structural responses to ventilator-induced lung injury: a multiscale...

Area of Science:

• Pulmonary Medicine
• Biomedical Engineering
• Pathology

Background:

• Mechanical ventilation (MV) can cause or worsen ventilator-induced lung injury (VILI).
• Heterogeneous lungs with pre-existing injury are particularly susceptible to VILI.
• Understanding VILI mechanisms in injured lungs is crucial for patient care.

Purpose of the Study:

• To investigate the structural and mechanical factors contributing to VILI in a rat model of bleomycin-induced lung injury.
• To correlate in-vivo lung mechanics with ex-vivo tissue properties.
• To elucidate the interplay between pre-existing lung injury and VILI.

Main Methods:

• Utilized a rat model with bleomycin-induced lung injury, compared to healthy controls.
• Employed a combined in-vivo and ex-vivo imaging approach, including 4D synchrotron micro-CT and forced oscillation measurements.
• Performed 3D pore analysis, atomic force microscopy (AFM), histology, and spatial co-registration on lung tissue.

Main Results:

• Injurious MV caused significant airspace enlargement, most pronounced in lungs with combined bleomycin injury and VILI.
• AFM revealed region-specific mechanical responses and linked pore geometry/stiffness to in-vivo mechanics.
• VILI-associated airspace damage spatially co-localized with regions of pre-existing lung injury and matrix remodeling.

Conclusions:

• Extracellular matrix remodeling influences lung response to injurious mechanical ventilation.
• VILI-induced lung damage preferentially occurs in areas with prior matrix injury.
• This multiscale approach offers mechanistic insights into VILI and informs ventilation strategies for structurally altered lungs.