In vivo imaging of canine lung deformation: Effects of posture, pneumonectomy, and inhaled erythropoietin.

Mechanical stresses on the lung impose the major stimuli for developmental and compensatory lung growth and remodeling. We used computed tomography (CT) to noninvasively characterize the factors influencing lobar mechanical deformation in relation to posture, pneumonectomy (PNX), and exogenous pro-angiogenic factor supplementation. Post-PNX adult canines received weekly inhalations of nebulized nanoparticles loaded with recombinant human erythropoietin (EPO) or control (empty nanoparticles) for 16 weeks. Supine and prone CT were performed at two transpulmonary pressures pre- and post-PNX following treatment. Lobar air and tissue volumes, fractional tissue volume (FTV), specific compliance (Cs), mechanical strains and shear distortion were quantified. From supine to prone, lobar volume and Cs increased while strain and shear magnitudes generally decreased. From pre- to post-PNX, air volume increased less and FTV and Cs increased more in the left caudal (LCa) than in other lobes. FTV increased most in the dependent subpleural regions and the portion of LCa lobe expand laterally wrapping around the mediastinum. Supine deformation was non-uniform pre- and post-PNX; strains and shear were most pronounced in LCa lobe and declined when prone. Despite non-uniform regional expansion and deformation, post-PNX lobar mechanics were well preserved compared to pre-PNX owing to robust lung growth and remodeling towards establishing a new mechanical equilibrium. EPO treatment eliminated posture-dependent changes in FTV, accentuated the post-PNX increase in FTV and reduced FTV heterogeneity without altering absolute air or tissue volumes, consistent with improved microvascular blood volume distribution and modestly enhanced post-PNX alveolar microvascular reserves.