Abstract
Introduction
The proposed pathophysiology of ventilator-induced lung injury (VILI) includes overdistension (volutrauma) and repetitive collapse and reopening (atelectrauma) of lung units. Using an isolated perfused mouse lung, we investigated the physiological and inflammatory consequences of these two mechanisms of VILI.
Methods
Isolated buffer-perfused lungs were ventilated with one of three protocols for 3 hours (n=5 each): ‘Control’ (7ml/kg tidal volume (VT), PEEP (5cmH2O) and regular sustained inflation (SI)); ‘Atelectasis’ (7ml/kg VT, zero PEEP without SI; ‘High-stretch’ (30-32ml/kg VT, PEEP (3cmH2O) with SI).
Results
Both injurious ventilation protocols led to increased peak inspiratory pressure (PIP; p<0.05 vs. start) and lavage protein (Table). High-stretch, but not atelectasis, increased perfusate cytokines compared to control. These increases were attenuated by monocyte depletion (achieved by pretreating animals with clodronate-liposomes), particularly TNF which was virtually abolished (302±69 vs. 20±14pg/ml; p<0.05). Monocyte depletion also attenuated stretch-induced PIP increase (p<0.05) and tended to reduce lavage protein (p=0.18).
Conclusion
These results strongly suggest that volutrauma, but not atelectrauma, activates lung-marginated monocytes leading to systemic cytokine release, which is a critical factor for multiple organ failure in ventilated critically-ill patients. Our findings may provide a novel explanation why open lung strategy seemingly has limited mortality benefits.
- © 2013 ERS