Please use this identifier to cite or link to this item:
|Author:||Reynolds, Ann Michelle|
|School/Discipline:||Dept. of Physiology|
|Abstract:||Hypocapnia-induced bronchoconstriction has been recognized for over J0 years, however, its nechanisms have to date renained essentially unknown. This thesis describes a guínea pig model of hypocapnia-induced bronchoconstriction and elucidates the mechanisms involved in this airway response. Despite the extensive use of guinea-pig isolated-lung preparations over past decades, severe postmortem bronchoconstriction in this species has only recently been described and has been observed in the prelininary studies of the present work reported herein. This phenomenon was re-examined by measuring postmortem airway function in anaesthetized open-chest guinea pigs following circulatory arrest, in an attenpt to determine the initiating factors. The intensity of bronchoconstriction was assessed by calculating changes in dynanic compliance and measuring relaxation lung volume at the completíon of the experiments. From these studies it was found that postnortem bronchoconstriction was principally due to airway hypocapnia, a known cause of bronchoconstriction. Changes in airway function were also observed if there was marked airway cooling and drying. Following the establishment of this guinea pig nodel of hypocapnia-induced bronchoconstriction, a second detailed stndy was undertaken to determine what mediators were involved. Tachykinins (a group of neuropeptides with a similar anino acid sequence at the C-terminal end) had recently been inplicated ín nediating guinea pig postmortem bronchoconstriction, thus raising the possibility that tachykinins may mediate the hypocapnia-induced bronchoconstriction observed ín this species. This second study was designed to determine whether hypocapnia causes bronchoconstriction by releasing tachykinins from C-afferent nerves in airways. Three experimental interventions were used: 1) depletion of tachykinins by repeated capsaicin injections, 2) treatnent with phosphoramidon, an inhibitor of enkephalinase, the main enzyne responsible for tachykinin inactivation, and 3) topical airway anaesthesia. Capsaicin pretreatment markedly attenuated the hypocapnia-induced changes ín dynanic compliance and relaxation lung volune whereas phosphoramidon auguented these changes. Topical anaesthesia of airways with bupivacaine almost completely prevented hypocapnia-induced bronchoconstriction. These studies demonstrate that in the guinea pig, postmortem bronchoconstriction is triggered by airway hypocapnl-a, and that this hypocapnia-induced bronchoconstriction is medíated by tachykinins which are released following the activatíon of bronchial axonal reflexes.|
|Dissertation Note:||Thesis (M. Sc.)--University of Adelaide, Dept. of Physiology, 1989.|
|Provenance:||This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals|
|Appears in Collections:||Research Theses|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.