The effect of acute alterations in oxygen tension on bronchoconstrictor and bronchodilator stimuli in-vitro in man and in-vivo in patients with asthma

Dagg, Kenneth D (2001) The effect of acute alterations in oxygen tension on bronchoconstrictor and bronchodilator stimuli in-vitro in man and in-vivo in patients with asthma. MD thesis, University of Glasgow.

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Abstract

An acute severe exacerbation of asthma is characterised by the release of inflammatory mediators, reduction in airway calibre and ultimately hypoxaemia. The initial management of such patients includes the administration of high concentrations of inspired oxygen and both nebulised and intravenous bronchodilators. Little however is known about the influence of oxygen tension on the responsiveness of airways to bronchodilator drugs and to bronchoconstrictor stimuli. Recent studies undertaken in our own laboratory have suggested that acute alterations in oxygen tension have profound effects on responses evoked by bronchodilators and bronchoconstrictors in isolated bronchial rings. Similar findings have been made in animals. Such observations in man may have relevance to the management of patients with acute exacerbations of asthma. The purpose of our studies was to investigate the influence of acute alterations in oxygen tension on bronchodilator and bronchoconstrictor stimuli both in-vitro in man and in-patients with asthma. Our initial in-vitro studies suggested that the ability of salbutamol to relax human bronchial rings is significantly attenuated by hypoxia (O2 tension 4%) when compared to normoxia (O2 tension 20%) and hyperoxia (O2 tension 95%). We also found that acute hypoxia (O2 tension 4%) significantly attenuated the ability of both histamine and methacholine to constrict human isolated bronchial rings when compared to nonnoxia (O2 tension 20%) and hyperoxia (O2 tension 95%). In-patients with mild asthma we found that hypoxia (FiO215%) potentiated and hyperoxia (FiO2100%) had no effect on methacholine induced bronchoconstriction. In a series of studies we have also found that airway responses to both inhaled histamine and salbutamol were unaffected by both hypoxia (FiO215%) and hyperoxia (FiO2 100%) in-patients with mild stable asthma. We would conclude from these studies that acute alterations in ambient oxygen tension have significant effects on airway responses to constrictor and dilator stimuli both in-vitro in man and in-patients with asthma. The finding that hypoxia potentiates both salbutamol induced relaxation in-vitro in man and methacholine induced bronchoconstriction in patients with asthma may have relevance to the management of patients with acute exacerbations asthma who as part of their routine treatment receive high inspired oxygen tensions and both nebulised and intravenous bronchodilators. Further studies may determine the mechanism of these effects and lead to the development on novel asthma therapies.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Neil Thomson
Keywords: Pharmacology
Date of Award: 2001
Depositing User: Enlighten Team
Unique ID: glathesis:2001-72138
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 12:49
Last Modified: 17 May 2019 12:49
URI: http://theses.gla.ac.uk/id/eprint/72138

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