Journal Article

Deterioration of Regional Lung Strain and Inflammation during Early Lung Injury

Winkler, Tilo, Harris, Robert S., Grogg, Kira, Santos, Arnoldo, Bajwa, Ednan, Baron, Rebecca M., Paula, Luís F. S. C., Motta-Ribeiro, Gabriel C., Vidal Melo, Marcos F., Hibbert, Kathryn, Hashimoto, Soshi, Zeng, Congli

2018

Overview

The contribution of aeration heterogeneity to lung injury during early mechanical ventilation of uninjured lungs is unknown. 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. 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 ( F-FDG) positron emission tomography. 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 F-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. F-FDG phosphorylation rate was associated with strain and blood volume. Imaging findings were confirmed in ventilated patients with sepsis. 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.

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Acute Lung Injury - diagnostic imaging / Acute Lung Injury - etiology / Acute Lung Injury - pathology / Analysis of Variance / Animals / Biopsy, Needle / Blood / Blood Gas Analysis / Clinical medicine / Disease Models, Animal / Endotoxemia - etiology / Endotoxemia - physiopathology / Endotoxins - pharmacology / Female / Fluorodeoxyglucose F18 / Gene expression / Homogenization / Humans / Hypotheses / Immunohistochemistry / Inflammation / Infusions, Intravenous / Intensive care / Linear Models / Lungs / Medical imaging / Multivariate Analysis / Original / Positron-Emission Tomography - methods / Pulmonary Atelectasis - diagnostic imaging / Pulmonary Atelectasis - etiology / Random Allocation / Respiration, Artificial - adverse effects / Respiration, Artificial - methods / Respiratory distress syndrome / Respiratory Distress Syndrome, Adult - diagnostic imaging / Respiratory Distress Syndrome, Adult - etiology / Respiratory Distress Syndrome, Adult - pathology / Respiratory Function Tests / Respiratory therapy / Risk Factors / Sepsis / Sheep / Tidal Volume - physiology / Time Factors / Tomography / Tomography, X-Ray Computed - methods / Ventilation / Ventilators