Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung

Abstract

Rationale Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathological process remains elusive. Objectives Describe Recruitment/Derecruitment (R/D) at acinar length scales over short time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of R/D, using a computational model. Methods Experiments were performed in anaesthetized rabbits ventilated in Pressure Controlled mode (PCV). The lung was consecutively imaged at ~1.5 min intervals, at each Positive End-Expiratory Pressure (PEEP) of 12, 9, 6, 3 and 0 cmH2O before and after injury. The extent and spatial distribution of R/D was analyzed by subtracting subsequent images. In a realistic lung structure we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and Recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points. Results Alternative R/D occurred in neighboring alveoli over short time scales in all tested PEEP levels and despite stable PCV. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at PEEP ≥ 3 cmH2O. Conclusions These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent R/D and subsequent lung damage.

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

“…This work underscores the merits of an extended inspiratory duration and a brief expiratory duration to improve alveolar recruitment and stability in a rat ARDS model [35], lung protection in a neonatal piglet model [58], and reduced ARDS incidence and mortality in trauma patients [59]. We postulate that as the lung opens, the increase in parenchymal tethering of airways [56] and alveolar interdependence [55] reduce lung pathology as a power-law function. Hamlington et al have shown that progressive lung injury advances in power-law fashion where alveolar R/D (atelectrauma) caused the initial holes in the epithelium and that high airway pressure (volutrauma) greatly expands these holes in a power-law or rich-get-richer fashion [60].…”

“…Synchrotron phase-contrast imaging can measure R/D at acinar length scales over short time frames and has demonstrated that lung collapse in the microenvironment differs between normal and acutely injured lungs [53][54][55][56]. Scaramuzzo et al first measured tissue collapse in the microenvironment of the normal lung with graded reductions in PEEP.…”

“…Before these critical pressures are obtained, there is no alveolar strain. However, the opening and closing pressures are not static; instead, they are dependent upon the level of surfactant deactivation and the degree of mechanical interdependence between adjacent alveolar walls and parenchymal tethering on the walls of small airways [55].…”

“…However, this computational model no longer supported the new biological evidence on R/D at the acinar level. An alveolar interdependence component was added to the model such that the closure of a unit will impact the critical opening and collapse pressures of adjacent units [55]. Fluid movement in the microenvironment during airway collapse and reopening suggests that the pressures necessary for opening and collapse are also a function of the time at which they are applied [56].…”

A Physiologically Informed Strategy to Effectively Open, Stabilize, and Protect the Acutely Injured Lung

“…This process progresses in an avalanche manner with power-law distributions of both the size of and intervals between avalanches (Suki et al, 1994;Alencar et al, 2002). It has been postulated that as the lung opens, the increase in parenchymal tethering of airways (Broche et al, 2017) and alveolar interdependence improves lung function as a power-law function (Nieman et al, 2019). These new perspectives inform the quest for novel protective ventilation strategies.…”