Interaction between regional lung volumes and ventilator induced lung injury in the normal and endotoxaemic lung

Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end expiratory lung volume exist that minimise lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxaemic lung. Adult female BALB/c mice were injected intraperitoneally with 10 mg.kg^-1 of lipopolysaccharide (LPS) in saline or saline alone. Four hours later, mice were mechanically ventilated for 2 hours. Regional specific end-expiratory volume (sEEV) and tidal volume (sVt) were measured at baseline and after 2 hours of ventilation using dynamic high-resolution 4DCT images. The regional expression of inflammatory genes was quantified by qPCR. There was a heterogenous response in regional sEEV whereby endotoxemia increased gas trapping at end-expiration in some lung regions. Within the healthy group, there was a relationship between sEEV, sVt and the expression of TNF-α where high Vt in combination with high EEV or very low EEV was associated with an increase in gene expression. In endotoxaemia there was an association between low sEEV, particularly when this was combined with moderate sVt, and high expression of IL-6. Our data suggest that pre-existing systemic inflammation modifies the relationship between regional lung volumes and inflammation and that, while optimum EEV-Vt combinations to minimise injury exist, further studies are required to identify the critical inflammatory mediators to assess and the effect of different injury types on the response.