PT  - JOURNAL ARTICLE
AU  - Kenji Wakabayashi
AU  - Michael Wilson
AU  - Kate Tatham
AU  - Kieran O'Dea
AU  - Masao Takata
TI  - High-stretch, but not atelectasis, causes systemic cytokine release by lung-marginated monocytes
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - P653
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/P653.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/P653.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - IntroductionThe 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.MethodsIsolated 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).ResultsBoth 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).ConclusionThese 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.View this table: