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The role of platelets and their associated recruitment mechanisms, in intestinal ischaemia reperfusion injury

Holyer, Ian (2011)
Ph.D. thesis, University of Birmingham.

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Recent studies have demonstrated a key role for platelets and microthrombi in the pathophysiology of intestinal ischaemia-reperfusion (IR) injury. The research described in this thesis investigates the role of the major platelet glycoprotein receptors in recruiting and activating platelets following intestinal IR injury, namely GPVI, GPIb-IX-V and the integrins IIb3 and 21. Intravital microscopy was utilised to monitor individual platelet adhesion and microthrombus formation in anaesthetised mice undergoing intestinal IR injury \(in\) \(vivo\) using a novel dual labelling methodology. This study focussed on the microcirculation of the mucosal villi as this luminal surface is most susceptible to IR injury. We demonstrate that it was necessary to inhibit both microthrombus formation as well as platelet-leukocyte-endothelial interactions in order to ensure longer lasting improvement in gut microcirculation and histology. This was achieved through a dual therapy that targeted both GPIb and P-selectin. The strongest anti-platelet effect was observed with blocking the IIb3 integrin, but this was also associated with a sustained bleeding from the mucosal surface. Overall, the research within this thesis suggests that therapeutic strategies targeting GPIb and P-selectin may prove beneficial in improving the clinical morbidity associated with gut IR injury.

Type of Work:Ph.D. thesis.
Supervisor(s):Watson, Steve P. and Kalid, Neena
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RB Pathology
RC Internal medicine
Institution:University of Birmingham
ID Code:1489
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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