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Title: The role of ischaemia-reperfusion on neutrophil activation in healthy humans
Author: Amoah, Vincent
ISNI:       0000 0004 2668 8659
Awarding Body: Coventry University
Current Institution: Coventry University
Date of Award: 2008
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Ischaemia-reperfusion injury is a common clinical event, still associated with high mortality and morbidity, and lacks a specific therapy. It is well established that postischaemic reflow is associated with the generation ofoxygen radicals, and that oxidant stress occurring during reperfusion may produce deleterious effects in reperfused tissue. A consistent feature oflocal tissue injury that follows ischaemiareperfusion injury is the histological fmding ofan acute inflammatory response mediated in part by increased vascular permeability, mast cell degranulation, plugging ofthe microvasculature by circulating leukocytes, with a concomitant recruitment of adherent and emigrating leukocytes, release ofreactive oxygen species and proteolytic enzymes, increased albumin extravasation in downstream postcapillary venules, and cell death. Ofthe different circulating cells activated, experimental models ofischaemia-reperfusion have identified the polymorphonuclear leukocyte (neutrophil) as mediating the initiation reperfusion-induced tissue injury. Research on ischaemia-reperfusion injury has focused on either animal studies or patients who are hospitalised. There is limited research on ischaemia-reperfusion in healthy individuals. Therefore, the aim ofthe series ofstudies set out was to investigate the functional response ofleukocytes ofhealthy individuals in response to ischaemia-reperfusion and from the results obtained to develop a working model of the mechanism involved in ischaemia-reperfusion. Male Participants (n = 125) (mean age 22 ± 4) all considered healthy were recruited from the university student population and the general public to participate in the study. Participants were exposed to ischaemia-reperfusion for various durations. Venous whole blood samples taken from the anticubital vein were subjected to various assays including the use ofluminol-enhanced chemiluminescence, and enzyme-linked immunosorbent assay with the aim ofdetermining the role, if any, that neutrophils play in ischaemia-reperfusion. From the results obtained from the series of studies it was demonstrated that reactive oxygen species production and neutrophil priming activation occur as a result ofischaemia-reperfusion, interacting possibly with each other and with other elements such as endothelial cells and other leukocytes. Further investigation is required to elucidate the mechanisms involved that lead to neutrophil activation, which will allow for the development ofnovel treatment to be developed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Not available Qualification Level: Doctoral
EThOS ID:  DOI: Not available