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Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice
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 Medical Sciences, Clinical Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2008 (English)In: Respiratory research (Online), ISSN 1465-993X, Vol. 9, no 23Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation. METHODS: Balb/c mice were sensitized to ovalbumin (OVA) and challenged with nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which was given twice during the minute before assessment of lung mechanics. RESULTS: DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8+/-0.3 to 2.8+/-0.1 cmH2O*s*mL-1 in healthy mice and 5.1+/-0.3 to 3.5+/-0.3 cmH2O*s*mL-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9+/-1.5% to 5.6+/-0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1+/-6.6% to 14.3+/-1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001). CONCLUSIONS: We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that presence of DI may blunt airway hyperreactivity.

Place, publisher, year, edition, pages
2008. Vol. 9, no 23
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-15680DOI: 10.1186/1465-9921-9-23ISI: 000254761300001PubMedID: 18307760OAI: oai:DiVA.org:uu-15680DiVA: diva2:43451
Available from: 2008-03-03 Created: 2008-03-03 Last updated: 2009-11-11Bibliographically approved
In thesis
1. Lung mechanics and airway inflammation in murine models of asthma
Open this publication in new window or tab >>Lung mechanics and airway inflammation in murine models of asthma
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Lungmekanik och luftvägsinflammation i djurmodeller för astma
Abstract [en]

Allergic asthma is an inflammatory disease of the airways and is characterized by eosinophilic inflammation and increased airway reactivity. In the studies presented in this thesis, lung mechanics and measurements of airway reactivity were assessed in anaesthetized tracheostomized mice by using an animal ventilator (flexiVent®). A forced oscillation technique makes it possible to measure of both airway and tissue mechanics with a potential to distinguish between central and peripheral airways. The results of the experiments on lung mechanics imply that it is important to understand how altered lung mechanics can affect the airway physiology in order to assess the relevance of different animal models of asthma. We have investigated the effects of changing different components of the lung mechanical measurements, such as administering bronchoconstrictive agents via inhalation or intravenously and implementing deep inhalation in animals with airway inflammation. We have also investigated the relation between airway inflammation and oxidative stress. We found that the formation and time-course of F2-isoprostanes, a marker of oxidative stress, and tissue damage were associated with the degree of inflammation and with the degree of heterogeneous airway airflow. Finally we wished to investigate the hypothesis that nitric oxide (NO) may interact with glucocorticoid (GC) treatment because we see a potential for finding new strategies to increase the therapeutic effect in poor responders or patients resistant to GC treatment. NO plays a central role in physiological regulation of the airway function, and is involved in asthma. We found that the concomitant administration of NO and GC attenuated the airway reactivity more than either treatment alone. In conclusion, with the information presented in this thesis, we hope to contribute to the development of better experimental tools and to improved understanding of murine models of asthma for investigating and understanding the underlying pathophysiology of asthma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 70 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 468
allergic asthma, airway inflammation, murine models, lung mechanics, forced oscillation technique, airway reactivity, deep inhalations, oxidative stress, nitric oxide, glucocorticoids.
National Category
Research subject
Clinical Physiology
urn:nbn:se:uu:diva-107061 (URN)978-91-554-7569-7 (ISBN)
Public defence
2009-09-11, Enghoffsalen, Akademiska Sjukhuset, Ingång 50, Uppsala, 13:15 (Swedish)
Available from: 2009-08-21 Created: 2009-07-15 Last updated: 2009-08-21Bibliographically approved

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Jonasson, SofiaLundqvist, MariaHedenstierna, GöranHjoberg, Josephine
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