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Comparisons of effects of intravenous and inhaled methacholine on airway physiology in a murine asthma model
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
2009 (English)In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 165, no 2-3, 229-236 p.Article in journal (Refereed) Published
Abstract [en]

Airway responses to intravenous (i.v.) and inhaled (i.h.) delivery of methacholine (MCh) in BALB/c and C57BL/6 mouse strains have been compared with and without ovalbumin (OVA)-induced airway inflammation. Bronchial reactivity to MCh was assessed in anaesthetised and tracheostomised animals by using an animal ventilator (flexiVent). We partitioned the response of the lungs into airway and parenchymal components in order to compare the contributions of the airways with those of the lung parenchyma to the pulmonary mechanical responses resulting from different routes of MCh administration. Our results indicate disparate physiological responses. Intravenous MCh delivery induced a higher maximum lung resistance than i.h. MCh in OVA-treated BALB/c mice but not in C57BL/6 mice. Inhaled MCh delivery led to a significantly larger fall in lung compliance and a greater impact on peripheral airways than i.v. MCh in both strains. In conclusion, i.v. and i.h. MCh produced disparate effects in different murine strains and variant responses in inflamed airways and healthy controls. The two methods of MCh delivery have important advantages but also certain limitations with regard to measuring airway reactivity in a murine model of allergic asthma.

Place, publisher, year, edition, pages
2009. Vol. 165, no 2-3, 229-236 p.
Keyword [en]
Lung mechanics, Airway reactivity, Asthma models, Murine strains, Ovalbumin, Airway inflammation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-99317DOI: 10.1016/j.resp.2008.12.005ISI: 000264579900017PubMedID: 19136080OAI: oai:DiVA.org:uu-99317DiVA: diva2:212333
Available from: 2009-04-21 Created: 2009-03-11 Last updated: 2017-12-13Bibliographically 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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 468
Keyword
allergic asthma, airway inflammation, murine models, lung mechanics, forced oscillation technique, airway reactivity, deep inhalations, oxidative stress, nitric oxide, glucocorticoids.
National Category
Physiology
Research subject
Clinical Physiology
Identifiers
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)
Opponent
Supervisors
Available from: 2009-08-21 Created: 2009-07-15 Last updated: 2009-08-21Bibliographically approved

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