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Evaluation of metabolism of adenosine triphosphate as a novel biomarker of tissue ischaemia in vivo.
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Fisher, Owain (2021) Evaluation of metabolism of adenosine triphosphate as a novel biomarker of tissue ischaemia in vivo. PhD thesis, University of Warwick.
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WRAP_Theses_Fisher_2021.pdf - Submitted Version - Requires a PDF viewer. Download (2709Kb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3518303~S15
Abstract
Introduction
Ischaemia is often a medical emergency, clinical signs and symptoms vary dependant on organ or organ system affected. Timely restoration of oxygen delivery to affected tissues is paramount to preventing morbidity and mortality. Current diagnostic aids are non-specific and often late markers of ischaemia where there has been irreversible tissue damage. Metabolism of adenosine triphosphate (ATP) is altered during periods of ischaemia and intermediate nucleosides such as adenosine, inosine and hypoxanthine are released into the systemic circulation in demonstrable quantities. Development of an amperometric biosensor sensitive to these purine nucleosides, produced early in ischaemia prior to cell death, gives potential for purine nucleosides to be a clinically relevant biomarker.
Methods
A series of prospective observational cohort studies have been designed to provide pilot data on purine nucleoside changes, measured in real-time in vivo in populations of both surgical and non-surgical patients where a simple test for early identification of ischaemia would be clinically useful expedite diagnosis and prevent patient harm.
Results
There was no significant variation from baseline readings in purine nucleosides in systemically obtained samples intra-operatively in patients who are anaesthetised with general anaesthetic. There were significant increases in nucleosides in blood samples obtained locally within acutely ischaemic tissue. Elevated purine nucleosides were also identified in patients with critical limb ischaemia and following some types of brain injury.
Conclusions
Reliable determination of purine nucleosides in vivo remains challenging; multiple factors may interfere with quantification in vivo. Results here have identified purine nucleosides may have a role in acute and chronic limb ischaemia as well as traumatic brain injury. This requires further validation in populations of patients in clinical practice. Expansion to further areas of ischaemia may also be of clinical value.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RB Pathology |
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Library of Congress Subject Headings (LCSH): | Metabolism, Adenosine triphosphate, Biochemical markers , Ischemia | ||||
Official Date: | 2021 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Imray, Christopher ; Hutchinson, Charles ; Benson, Ruth | ||||
Format of File: | |||||
Extent: | 194 leaves: illustrations, plates, charts. | ||||
Language: | eng |
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