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Role of glucose, acetate and plasma in the maintenance of mitochondrial function, energy metabolism and cell integrity during platelet storage in additive solutions

Saunders, Christine V. 2012. Role of glucose, acetate and plasma in the maintenance of mitochondrial function, energy metabolism and cell integrity during platelet storage in additive solutions. PhD Thesis, Cardiff University.
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Abstract

A potential benefit of the use of artificial media for the suspension of platelets as concentrates is a reduction of the morphological, functional and metabolic changes observed in platelets during storage and collectively referred to as the platelet storage lesion (PSL). A better understanding of the nature of the PSL may suggest strategies for manipulation of the storage environment to improve platelet viability and efficacy posttransfusion. In this context, two principal considerations formed the basis for the study: · The hypothesis that apoptosis is a central mechanism responsible for the changes observed in the PSL. · The investigation of this hypothesis within the applied setting of improving the storage environment of platelet concentrates. The study investigated the role on the PSL of plasma protein (in the form of albumin), acetate and glucose in leucoreduced platelet concentrates suspended in a medium with minimal plasma. A 14-day storage study on platelet concentrates in either plasma or a 70:30 ratio of a commercial additive solution (SSP+Ô) and plasma provided an overview of platelet in vitro characteristics under standard storage conditions. The work led to targeted investigations into the nature of the cell death mechanism in platelet concentrates. Results suggested that in storage media with adequate energy stores, a Bcl-2 proteinmediated mechanism of cell death was viable, though possibly storage-time dependent and limited by pre-existing levels of anti-apoptotic Bcl-2 proteins in the platelets. Further studies would be required to determine if this mechanism is akin to caspasedependent apoptosis. In media lacking glucose, a mechanism more reminiscent of necrosis was observed, associated with decreased ATP levels, accelerated mitochondrial dysfunction, elevated intracellular free calcium and culminating in platelet disruption.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: Q Science > QP Physiology
R Medicine > R Medicine (General)
Date of First Compliant Deposit: 30 March 2016
Last Modified: 19 Mar 2016 23:19
URI: http://orca.cf.ac.uk/id/eprint/47076

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