Deterioration of regional lung strain and inflammation during early lung injury

Rationale: The contribution of aeration heterogeneity to lung injury during early mechanical ventilation of uninjured lungs is unknown. Objectives: To test the hypotheses that a strategy consistent with clinical practice does not protect from worsening in lung strains during the first 24 hours of ventilation of initially normal lungs exposed to mild systemic endotoxemia in supine versus prone position, and that local neutrophilic inflammation is associated with local strain and blood volume at global strains below a proposed injurious threshold. Methods: Voxel-level aeration and tidal strain were assessed by computed tomography in sheep ventilatedwith lowVT and positive endexpiratory pressure while receiving intravenous endotoxin. Regional inflammation and blood volumewere estimated from2-deoxy-2-[(18)F] fluoro-D-glucose (¹⁸F-FDG) positron emission tomography. Measurements and Main Results: Spatial heterogeneity of aeration and strain increased only in supine lungs (P < 0.001), with higher strains and atelectasis than prone at 24 hours. Absolute strains were lower than those considered globally injurious. Strains redistributed to higher aeration areas as lung injury progressed in supine lungs. At 24 hours, tissue-normalized ¹⁸F-FDG uptake increasedmore in atelectatic andmoderately high-aeration regions (>70%) than in normally aerated regions (P < 0.01), with differential mechanistically relevant regional gene expression. ¹⁸F-FDGphosphorylation rate was associated with strain and blood volume. Imaging findings were confirmed in ventilated patients with sepsis. Conclusions: Mechanical ventilation consistent with clinical practice did not generate excessive regional strain in heterogeneously aerated supine lungs. However, it allowed worsening of spatial strain distribution in these lungs, associated with increased inflammation. Our results support the implementation of early aeration homogenization in normal lungs.