Inflammatory Activity in Atelectatic and Normally Aerated Regions During Early Acute Lung Injury

Rationale and Objectives: Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[¹⁸F]-fluoro-D-glucose (¹⁸F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury. Materials and Methods: We studied supine sheep in four groups: Permissive Atelectasis (n = 6)—16 hours protective tidal volume (V_T) and zero positive end-expiratory pressure; Mild (n = 5) and Moderate Endotoxemia (n = 6)- 20–24 hours protective ventilation and intravenous lipopolysaccharide (Mild = 2.5 and Moderate = 10.0 ng/kg/min), and Surfactant Depletion (n = 6)—saline lung lavage and 4 hours high V_T. Measurements performed immediately after anesthesia induction served as controls (n = 8). Atelectasis was defined as regions of gas fraction <0.1 in transmission or computed tomography scans. ¹⁸F-FDG kinetics measured with positron emission tomography were analyzed with a three-compartment model. Results: ¹⁸F-FDG net uptake rate in atelectatic tissue was larger during Moderate Endotoxemia (0.0092 ± 0.0019/min) than controls (0.0051 ± 0.0014/min, p = 0.01). ¹⁸F-FDG phosphorylation rate in atelectatic tissue was larger in both endotoxemia groups (0.0287 ± 0.0075/min) than controls (0.0198 ± 0.0039/min, p = 0.05) while the ¹⁸F-FDG volume of distribution was not significantly different among groups. Additionally, normally aerated regions showed larger ¹⁸F-FDG uptake during Permissive Atelectasis (0.0031 ± 0.0005/min, p < 0.01), Mild (0.0028 ± 0.0006/min, p = 0.04), and Moderate Endotoxemia (0.0039 ± 0.0005/min, p < 0.01) than controls (0.0020 ± 0.0003/min). Conclusion: Atelectatic regions present increased metabolic activation during moderate endotoxemia mostly due to increased ¹⁸F-FDG phosphorylation, indicative of increased cellular metabolic activation. Increased ¹⁸F-FDG uptake in normally aerated regions during permissive atelectasis suggests an injurious remote effect of atelectasis even with protective tidal volumes.