Design of a new variable-ventilation method optimized for lung recruitment in mice

Variable ventilation (VV), characterized by breath-to-breath variation of tidal volume (V-T) and breathing rate (f), has been shown to improve lung mechanics and blood oxygenation during acute lung injury in many species compared with conventional ventilation (CV), characterized by constant V-T and f. During CV as well as VV, the lungs of mice tend to collapse over time; therefore, the goal of this study was to develop a new VV mode (VVN) with an optimized distribution of V-T to maximize recruitment. Groups of normal and HCl-injured mice were subjected to 1 h of CV, original VV (VVO), CV with periodic large breaths (CVLB), and VVN, and the effects of ventilation modes on respiratory mechanics, airway pressure, blood oxygenation, and IL-1 beta were assessed. During CV and VVO, normal and injured mice showed regional lung collapse with increased airway pressures and poor oxygenation. CVLB and VVN resulted in a stable dynamic equilibrium with significantly improved respiratory mechanics and oxygenation. Nevertheless, VVN provided a consistently better physiological response. In injured mice, VVO and VVN, but not CVLB, were able to reduce the IL-1 beta-related inflammatory response compared with CV. In conclusion, our results suggest that application of higher V-T values than the single V-T currently used in clinical situations helps stabilize lung function. In addition, variable stretch patterns delivered to the lung by VV can reduce the progression of lung injury due to ventilation in injured mice.