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 ventilated with low Vt and positive end-expiratory pressure while receiving intravenous endotoxin. Regional inflammation and blood volume were estimated from 2-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 increased more in atelectatic and moderately high-aeration regions (>70%) than in normally aerated regions (P < 0.01), with differential mechanistically relevant regional gene expression. 18F-FDG phosphorylation 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.
['Motta-Ribeiro|Gabriel C|GC|0000-0001-5982-8863', 'Hashimoto|Soshi|S|', 'Winkler|Tilo|T|0000-0002-7276-5550', 'Baron|Rebecca M|RM|', 'Grogg|Kira|K|', 'Paula|Luís F S C|LFSC|', 'Santos|Arnoldo|A|', 'Zeng|Congli|C|', 'Hibbert|Kathryn|K|', 'Harris|Robert S|RS|', 'Bajwa|Ednan|E|', 'Vidal Melo|Marcos F|MF|']
D055371:Acute Lung Injury D000704:Analysis of Variance D000818:Animals D001707:Biopsy, Needle D001784:Blood Gas Analysis D004195:Disease Models, Animal D019446:Endotoxemia D004731:Endotoxins D005260:Female D019788:Fluorodeoxyglucose F18 D006801:Humans D007150:Immunohistochemistry D007262:Infusions, Intravenous D016014:Linear Models D015999:Multivariate Analysis D049268:Positron-Emission Tomography D001261:Pulmonary Atelectasis D011897:Random Allocation D012121:Respiration, Artificial D012128:Respiratory Distress Syndrome D012129:Respiratory Function Tests D012307:Risk Factors D012756:Sheep D013990:Tidal Volume D013997:Time Factors D014057:Tomography, X-Ray Computed
mechanical ventilation endotoxemia acute respiratory distress syndrome positron emission tomography computed tomography ventilator-induced lung injury