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Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2014 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 5, 505- p.Article in journal (Refereed) Published
Abstract [en]

Introduction

When alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.

Methods

A total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.

Results

Atelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.

Conclusions

The present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.

Place, publisher, year, edition, pages
2014. Vol. 18, no 5, 505- p.
National Category
Clinical Medicine
Research subject
Clinical Physiology
Identifiers
URN: urn:nbn:se:uu:diva-233429DOI: 10.1186/s13054-014-0505-1ISI: 000351850600024PubMedID: 25200702OAI: oai:DiVA.org:uu-233429DiVA: diva2:752461
Available from: 2014-10-03 Created: 2014-10-03 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Aspects on ventilation induced stress and strain on regional and global inflammation in experimental acute respiratory distress syndrome
Open this publication in new window or tab >>Aspects on ventilation induced stress and strain on regional and global inflammation in experimental acute respiratory distress syndrome
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mechanical ventilation (MV) is a life-saving therapy in acute respiratory distress syndrome (ARDS), a condition that affects 3000 patients/year in Sweden with a mortality rate of about 40%. However, MV may induce or worsen lung injury causing “ventilator-induced lung injury (VILI)”. From a mechanical perspective strain (deformation, or relative change in lung volume) and stress (tension) have been postulated as main determinants of VILI. High respiratory rate is potentially another factor that may exacerbate VILI by amplifying the total energy transmitted to the lungs during MV. In this thesis in animal ARDS models the hypotheses were that 1) lung parenchyma inhomogeneities concentrate stress and amplify lung damage and inflammation, 2) higher respiratory rates increase lung inflammation and lung edema in heterogeneous ARDS, and 3) local lung deformation is related to local inflammation.

First, in a rat model the effect on inflammation and structural damage of regional lung collapse on the healthy surrounding lung tissue was assessed. Second, in porcine models the effect of respiratory rate on lung edema and inflammation was studied during two ventilatory modes; a) a permissive collapse mode and b) a homogenized lung parenchyma mode. Finally, lung deformation was correlated with lung inflammation assessed by positron emission tomography using 18F-FDG uptake.

It was found that; 1) local inhomogeneities can act as stress amplifiers, increasing lung tissue inflammation and damage in the healthy surrounded lung. 2) high respiratory rate increases lung edema but decreases lung inflammation when permissive lung collapse is used and that these effects are prevented with lung parenchyma homogenization; 3) local lung deformation and inflammation are well correlated.

In conclusion, lung inhomogeneities may aggravate VILI, respiratory rate may affect in different ways VILI progression depending on the ventilatory strategy, and finally, lung deformation is closely related to lung inflammation. With the caveat that the studies are performed in animal models, the results suggest that using ventilator strategies that homogenize the lungs, i.e., open collapsed lung regions and prevent re-collapse in ARDS will reduce VILI and in the end may decrease morbidity and the high mortality in this condition.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1235
Keyword
ARDS, VILI, respiratory rate, strain, PET
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-296952 (URN)978-91-554-9612-8 (ISBN)
External cooperation:
Public defence
2016-09-06, Hedstrandsalen, Akademiska sjukhuset, Ing 70, 751 85 Uppsala, UPPSALA, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Heart Lung Foundation, K2015-99X-22731-01-4
Available from: 2016-08-16 Created: 2016-06-20 Last updated: 2016-08-25

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Retamal, JaimeBatista Borges, JoãoLarsson, AndersHedenstierna, Göran

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