Assessing the Progression of Ventilator-Induced Lung Injury in Mice

Patients with acute respiratory distress syndrome receiving mechanical ventilation typically experience repetitive closure (derecruitment) and subsequent reopening (recruitment) of airways and alveoli. This can lead, over time, to further ventilator-induced lung injury (VILI). Recruitment and derecruitment (R/D) thus reflect both the current level of lung injury and the risk for sustaining further injury. Accordingly, we investigated how the dynamics of R/D are altered as VILI develops following application of high tidal volume ventilation in initially healthy mice. R/D occurring on subsecond timescales was assessed from the shape of the pressure-volume ( PV) loop measured during a single large breath. R/D occurring on a timescale of minutes was evaluated via a derecruitability test in which we tracked the progressive increases in lung elastance occurring during periods of mechanical ventilation immediately following a recruitment maneuver. The degrees of R/D occurring on these different times scales were strongly correlated. To interpret these findings in quantitative terms, we developed a computational model of the lung in which changes in lung volume occurred both via R/D and distention of already open lung units. Fitting this model to measured PV loops indicates that VILI causes R/D both to increase and to occur at progressively higher pressures, and that the lung tissue that remains open during the breath becomes progressively more overdistended. We conclude that the dynamic PV loop in conjunction with our computational model can be used to assess the current injury state of the lung as well as its likelihood of sustaining further VILI.