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Title: Development and validation of an isolated large animal bladder model to study the integrative physiology of the bladder
Author: Parsons, Brian Andrew
ISNI:       0000 0004 5915 9710
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Bladder function is more intricate than first thought and knowledge of its integrat ive physiology remains incomplete. In vitro research using muscle strips and isolated cells have been central to our current understanding, but these approaches fa il to reproduce the complex network of cell-cell interactions that underpin normal bladder function. Some of these shortcomings have been addressed by using whole organ preparations, but most of this work has been done with bladders harvested from rodents and small mammals. Extrapolating findings generated using small laboratory animals to the lower urinary tract physiology of large animals and to the clinical context is difficult, and requires careful validation. This highlights the need for a validated large animal bladder model. Studies have demonstrated comparable urodynamic and structural characteristics between pigs and humans. Using the pig's native vasculature, a pump-perfusion system was developed to maintain viability of isolated bladders by overcoming the short molecular diffusion distance that restricts transmural permeation of nutrients and oxygen. A reproducible experimental approach was established and the model was validated through pharmacological experiments and using histological techniques. Proof of concept studies looking at autonomous activity, bladder wall movements and assessing the role of ion channels in mediating contraction were performed to highlight the potential use of this model for studying physiological aspects of bladder function. This research has confirmed that isolated large animal bladder viability can be maintained for prolonged periods of time, despite limited warm and cold ischaemia. Measured pharmacological responses indicate that the perfused bladder is kept in a functional condition, allowing its use in assessing detrusor function. This experimental approach provides new potential for elucidating the functional complexities of integrative bladder physiology. The use of different routes for drug administration (intravascular, intravesical and serosal) may help discern the relative contribution of different cell types within the bladder wall.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available