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

Takuga Hinoshita; Gabriel Motta Ribeiro; Tilo Winkler; Nicolas de Prost; Mauro R Tucci; Eduardo Leite Vieira Costa; Tyler J Wellman; Soshi Hashimoto; Congli Zeng; Alysson R Carvalho; Marcos Francisco Vidal Melo

doi:10.1016/j.acra.2019.12.022

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

Acad Radiol. 2020 Dec;27(12):1679-1690. doi: 10.1016/j.acra.2019.12.022. Epub 2020 Mar 12.

Affiliations

¹ Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St. Boston, MA; Tokyo Medical and Dental University, Department of Intensive Care Medicine, Tokyo, Japan. Electronic address: dr.takuga@gmail.com.
² University of São Paulo, Cardio-Pulmonary Department, São Paulo, Brazil.
³ Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St. Boston, MA.
⁴ Hôpital Henri Mondor, Medical Intensive Care Unit, Créteil, France.
⁵ Hospital das Clínicas, Faculdade de Medicina, São Paulo, Brasil.
⁶ inviCRO, LLC, Boston, Massachusetts.
⁷ Kyoto Okamoto Memorial Hospital, Department of Anesthesiology, Kyoto, Japan.
⁸ Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St. Boston, MA; The First Affiliated Hospital, Department of Anesthesiology and Intensive Care, Zhejiang Sheng, China.
⁹ Carlos Chagas Filho Institute of Biophysics, Laboratory of Respiration Physiology, Rio de Janeiro, Brazil.

Abstract

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.

Keywords: (18)F-FDG PET; Acute lung injury; Atelectasis; Endotoxin; Mechanical ventilation.

MeSH terms

Acute Lung Injury* / diagnostic imaging
Animals
Fluorodeoxyglucose F18
Lung
Positron-Emission Tomography
Respiration, Artificial*
Sheep

Substances

Fluorodeoxyglucose F18

Grants and funding

R01 HL121228/HL/NHLBI NIH HHS/United States