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Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure
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.
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 Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
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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.

Place, publisher, year, edition, pages
2013. Vol. 115, no 10, 1464-1473 p.
Keyword [en]
small airways dysfunction, absorption atelectasis, acute respiratory distress syndrome
National Category
Medical and Health Sciences Physiology
Identifiers
URN: urn:nbn:se:uu:diva-213823DOI: 10.1152/japplphysiol.00763.2013ISI: 000327398600007OAI: oai:DiVA.org:uu-213823DiVA: diva2:683599
Available from: 2014-01-05 Created: 2014-01-04 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography
Open this publication in new window or tab >>Regional Lung Kinetics of Ventilator-Induced Lung Injury and Protective-Ventilation Strategies Studied by Dynamic Positron Emission Tomography
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
[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:nbn:se:uu:diva-230022 (URN)978-91-554-9003-4 (ISBN)
Public defence
2014-10-03, Enghoffsalen, Akademiska sjukhuset, Uppsala, 09:00 (English)
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Available from: 2014-09-12 Created: 2014-08-19 Last updated: 2017-09-11Bibliographically approved

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Borges, João BatistaLarsson, AndersHedenstierna, Göran

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