Alveolar Micromechanics in Bleomycin-induced Lung Injury

Abstract

Lung injury results in intratidal alveolar recruitment and derecruitment and alveolar collapse, creating stress concentrators that increase strain and aggravate injury. In this work, we sought to describe alveolar micromechanics during mechanical ventilation in bleomycin-induced lung injury and surfactant replacement therapy. Structure and function were assessed in rats 1 day and 3 days after intratracheal bleomycin instillation and after surfactant replacement therapy. Pulmonary system mechanics were measured during ventilation with positive end-expiratory pressures (PEEPs) between 1 and 10 cm HO, followed by perfusion fixation at end-expiratory pressure at airway opening (Pao) values of 1, 5, 10, and 20 cm HO for quantitative analyses of lung structure. Lung structure and function were used to parameterize a physiologically based, multicompartment computational model of alveolar micromechanics. In healthy controls, the numbers of open alveoli remained stable in a range of Pao = 1-20 cm HO, whereas bleomycin-challenged lungs demonstrated progressive alveolar derecruitment with Pao < 10 cm HO. At Day 3, ∼40% of the alveoli remained closed at high Pao, and alveolar size heterogeneity increased. Simulations of injured lungs predicted that alveolar recruitment pressures were much greater than the derecruitment pressures, so that minimal intratidal recruitment and derecruitment occurred during mechanical ventilation with a tidal volume of 10 ml/kg body weight over a range of PEEPs. However, the simulations also predicted a dramatic increase in alveolar strain with injury that we attribute to alveolar interdependence. These findings suggest that in progressive lung injury, alveolar collapse with increased distension of patent (open) alveoli dominates alveolar micromechanics. PEEP and surfactant substitution reduce alveolar collapse and dynamic strain but increase static strain.

The micromechanics of lung alveoli: structure and function of surfactant and tissue components

“…transpulmonary pressure gradients below 10 cm H 2 O) volume changes predominantly take place in alveolar ducts while a smaller proportion of volume change takes place in the alveoli (Sera et al 2013; Mercer et al 1987; Knudsen et al 2010, 2018). During spontaneous breathing it has been estimated from synchrotron X-ray imaging that 34% of tidal volume results in an increase of alveolar volume while the remaining 66% end up in the ductal or conducting airspaces during inspiration (Chang et al 2015).…”

“…4 The stress-bearing elements of acinar airspaces. In a previous study (Knudsen et al 2018 ), healthy rat lungs were fixed in vivo at airway opening pressure (Pao) of 1 ( a ) and 10 cm H 2 O ( b ). At low pressure, the alveolar ducts are narrow and the inter-alveolar septal walls are characterized by foldings and pleats.…”

Prevention and treatment of acute lung injury with time-controlled adaptive ventilation: physiologically informed modification of airway pressure release ventilation

“…More recent studies suggest that the lung pathology compartmentalized by gravity (i.e., normal lung tissue adjacent to acutely injured tissue) is incorrect and that regional lung strain and inflammation throughout the entire lung is the main driver of VILI [16,[31][32][33][34][35][36]. Regional strain is caused with each breath by (1) alveolar and alveolar duct R/D [37][38][39][40][41][42][43] and (2) stress-multiplication (S-M), which cause injury to open lung areas adjacent to collapsed or edema-filled tissue [18,19,[44][45][46][47][48]. Retamal et al used CT scans to generate volumetric strain maps revealing highly heterogeneous regional strains (caused by alveolar R/D and S-M), which suggests that there may not be a safe threshold for low Vt [49].…”

Mechanical Ventilation Lessons Learned From Alveolar Micromechanics

“…Pressure-volume curves have also been shown to be a suboptimal indicator of alveolar recruitment and derecruitment (Dirocco et al, 2007). The ventilator calculates the respiratory system compliance [Vt/(P Plat -PEEP)] but does not partition out lung and chest wall compliance (Hess, 2014) where the lung compliance is impacted by alveolar stability Knudsen et al, 2018). The lung compliance as a single value may not account for the regional and alveolar heterogeneity associated with the injured lung (Kollisch-Singule et al, 2016), with discordant alveolar compliance even in adjacent alveoli (Perlman et al, 2011;Broche et al, 2017).…”