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Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mechanical ventilation in itself can harm the lung and cause ventilator-induced lung injury (VILI), which can induce or aggravate acute respiratory distress syndrome (ARDS). Much debate remains over pivotal concepts regarding the pathophysiology of VILI, especially about the precise contribution, kinetics, and primary role of potential VILI mechanisms. Consequently, it remains largely unknown how best to design a well-timed and full-bodied mechanical ventilation strategy. Little is known also about small airways dysfunction in ARDS. Dynamic positron emission tomography (PET) with [18F]fluoro-2-deoxy-D-glucose (18F-FDG) can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We studied the regional evolution of inflammation using dynamic PET/CT imaging of 18F-FDG in VILI and during different lung-protective mechanical ventilation strategies. By dynamic CT we investigated also the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction. Piglets were submitted to an experimental model of early ARDS combining repeated lung lavages and injurious mechanical ventilation. The animals were subsequently studied during sustained VILI, or submitted to distinct approaches of lung-protective mechanical ventilation: the one recommended by the ARDS Network (ARDSNet), or to one defined as open lung approach (OLA). The normally and poorly aerated regions - corresponding to intermediate gravitational zones - were the primary targets of the inflammatory process accompanying early VILI, which may be attributed to the small volume of the aerated lung that receives most of ventilation. The ARDSNet strategy did not attenuate global pulmonary inflammation during 27h and led to a concentration of inflammatory activity in the upper and poorly aerated lung regions. The OLA, in comparison with the ARDSNet approach, resulted in sustained and better gas exchange and lung mechanics. Moreover, the OLA strategy resulted in less global and regional inflammation. Dynamic CT data suggested that a significant amount of airway closure and related reabsorption atelectasis occurs in acute lung injury. Whether potential distal bronchioles injury (“bronchiolotrauma”) is a critical and decisive element in ventilator-associated lung injury is a matter for future studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. , 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1018
Keyword [en]
[18F]fluoro-2-deoxy-D-glucose; positron emission tomography; acute pulmonary inflammation; acute respiratory distress syndrome; mechanical ventilation; ventilator-induced lung injury
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-230022ISBN: 978-91-554-9003-4 (print)OAI: oai:DiVA.org:uu-230022DiVA: diva2:738740
Public defence
2014-10-03, Enghoffsalen, Akademiska sjukhuset, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2014-09-12 Created: 2014-08-19 Last updated: 2017-09-11Bibliographically approved
List of papers
1. Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
Open this publication in new window or tab >>Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury
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2014 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 42, no 4, e279-e287 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [F]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 [F]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 [F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration.

MEASUREMENTS AND MAIN RESULTS: [F]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 [F]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 [F]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.

National Category
Medical and Health Sciences
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-223348 (URN)10.1097/CCM.0000000000000161 (DOI)000332839700003 ()24448197 (PubMedID)
Available from: 2014-04-17 Created: 2014-04-17 Last updated: 2017-12-05Bibliographically approved
2. Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
Open this publication in new window or tab >>Lung inflammation persists after 27 hours of protective ARDSNet strategy and concentrated in the nondependent lung.
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-230045 (URN)
Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2015-01-22Bibliographically approved
3. Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
Open this publication in new window or tab >>Molecular Imaging in an Animal Model of Early Acute Respiratory Distress Syndrome: Rethinking the Lung-Protective Mechanical Ventilation Strategy
(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-230046 (URN)
Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2015-01-22Bibliographically approved
4. Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
Open this publication in new window or tab >>Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
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2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, 1464-1473 p.Article in journal (Refereed) Published
Abstract [en]

Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

Keyword
small airways dysfunction, absorption atelectasis, acute respiratory distress syndrome
National Category
Medical and Health Sciences Physiology
Identifiers
urn:nbn:se:uu:diva-213823 (URN)10.1152/japplphysiol.00763.2013 (DOI)000327398600007 ()
Available from: 2014-01-05 Created: 2014-01-04 Last updated: 2017-12-06Bibliographically approved

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