Modeling the effects of stretch-dependent surfactant secretion on lung recruitment during variable ventilation

Abstract

Variable ventilation (VV) is a novel strategy of ventilatory support that utilizes random variations in the delivered tidal volume ( V T ) to improve lung function. Since the stretch pattern during VV has been shown to increase surfactant release both in animals and cell c ulture, we hypothesized that there were combination s of PEEP and V T during VV that led to improved alveolar recruitment compared to conventional mechanical ventilation (CV). To test this hypothesis, we developed a computational model of stretch-induced surfactant release combined with abnormal alveolar mechanics of the injured lung under mechanical ventilation. We modeled the lung as a set of distinct acini with independent surfactant secretion and thus pressure-volume relationships. The rate of surfactant secretion was modulated by the stretch magnitude that an alveolus experienced per breath. Mechanical ventilation was simulated by delivering a prescribed V T at each breath. The fractional V T that each acinus received depended on its local compliance relative to the total system compliance. Regional variability in V T thus developed through feedback between stretch and surfactant release and coupling of regional V T to ventilator settings. The model allowed us to simulate patient-ventilator interactions over a wide range of PEEPs and V T s during CV and VV. Full recruitment was achieved through VV at a lower PEEP than required for CV. During VV, the acini were maintained under non-equilibrium steady-state conditions with breath-by-breath fluctuations of regional V T . In CV, alveolar injury was prevented with high-PEEP-low- V T or low-PEEP-high- V T combinations. In contrast, one contiguous region of PEEP- V T combinations allowed for full recruitment without overdistention during VV. We found that maintaining epithelial cell stretch above a critical threshold with either PEEP or V T may help stabilize the injured lung. These results demonstrate the significance of patient-ventilator cou pling through the influence of cellular stretch-induced surfactant release on the whole lung stability.