Numerical Model of the Respiratory Modulation of Pulmonary Shunt and PaO₂ Oscillations for Acute Lung Injury

It is an accepted hypothesis that the amplitude of the respiratory-related oscillations of arterial partial pressure of oxygen (ΔPaO₂) is primarily modulated by fluctuations of pulmonary shunt (Δs), the latter generated mainly by cyclic alveolar collapse/reopening, when present. A better understanding of the relationship between ΔPaO₂, Δs, and cyclic alveolar collapse/reopening can have clinical relevance for minimizing the severe lung damage that the latter can cause, for example during mechanical ventilation (MV) of patients with acute lung injury (ALI). To this aim, we numerically simulated the effect of such a relationship on an animal model of ALI under MV, using a combination of a model of lung gas exchange during tidal ventilation with a model of time dependence of shunt on alveolar collapse/opening. The results showed that: (a) the model could adequately replicate published experimental results regarding the complex dependence of ΔPaO₂ on respiratory frequency, driving pressure (ΔP), and positive end-expiratory pressure (PEEP), while simpler models could not; (b) such a replication strongly depends on the value of the model parameters, especially of the speed of alveolar collapse/reopening; (c) the relationship between ΔPaO₂ and Δs was overall markedly nonlinear, but approximately linear for PEEP ≥ 6 cmH₂O, with very large ΔPaO₂ associated with relatively small Δs.