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Early Inflammation Mainly Affects Normally and Poorly Aerated Lung in Experimental Ventilator-Induced Lung Injury*

Borges, João Batista MD, PhD1,2; Costa, Eduardo L. V. MD, PhD2,3; Suarez-Sipmann, Fernando MD, PhD1,4; Widström, Charles MSc5; Larsson, Anders MD, PhD1; Amato, Marcelo MD, PhD2; Hedenstierna, Göran MD, PhD6

doi: 10.1097/CCM.0000000000000161
Online Laboratory Investigations

Objective: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [18F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [18F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome.

Design: Prospective laboratory investigation.

Setting: A university animal research laboratory.

Subjects: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls.

Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

Measurements and Main Results: [18F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [18F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [18F]fluoro-2-deoxy-D-glucose uptakes similar to controls.

Conclusions: The present findings suggest that normally and poorly aerated regions—corresponding to intermediate gravitational zones—are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

1Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.

2Pulmonary Divison, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

3Research and Education Institute, Hospital Sírio Libanês, São Paulo, Brazil.

4Centros de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

5Department of Hospital Physics, Uppsala University Hospital, Uppsala, Sweden.

6Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

* See also p. 1010.

This work was performed at Uppsala University, Uppsala, Sweden.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (São Paulo State Research Support Foundation), Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development), Financiadora de Estudos e Projetos (Studies and Projects Financial Support Provider), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Ministry of Education, Brazil, and also institutional funds from Uppsala University, Swedish Research Council—5315 and Swedish Heart-Lung Fund, Sweden.

Dr. Borges received grant support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Ministry of Education, Brazil. Dr. Suarez-Sipmann consulted for Maquet Critical Care and received grant support from Fondo de investigación Sanitaria and Centros de Investigación Biomédica en Red de Enfermedades Respiratorias. Dr. Larsson received grant support from the Swedish Heart Lung foundation, consulted for Maquet CC, lectured for GE health care, and received support for travel from Eli-lilly and Maquet. Dr. Amato received grant support from Fundação de Amparo a Pesquisa do Estado de São Paulo (São Paulo State Research Support Foundation), Brazil, and Financiadora de Estudos e Projetos (Studies and Projects Financial Support Provider), Brazil. Dr. Hedenstierna received grant support and support for travel from the Swedish Research Council and received support for article research from Swedish research Council and Uppsala University. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: joao.batista_borges@medsci.uu.se

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins