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Title: Apoptosis and necrosis in ischaemia/reoxygenation injury of the human myocardium : mechanism of protection by ischaemic preconditionng
Authors: Vohra, Hunaid Ahmed
Award date: 2005
Presented at: University of Leicester
Abstract: Gene ChipRTM microarrays were used to analyse mRNA isolated from right atrial appendages (n=3/group) subjected to SI/R, IPC and caspase-3 inhibition. The initial studies were carried out with specific ischaemia/reoxygenation time-points. Apoptosis was shown to be greater than necrosis after 90min simulated ischaemia (SI) and 8h reoxygenation (R) but necrosis was greater than apoptosis by 24hr R. Inhibition of caspase-8+9 by z.IETD.fmk+z.LEHD.fmk (70nM) significantly reduced apoptosis following 90min SI and 2hr R and inhibition of caspase-3 by z.DEVD.fmk (70nM) almost completely abolished apoptosis, both without effecting necrosis. I have also shown that ischaemic preconditioning (IPC) is more efficacious in reducing apoptosis than necrosis. IPC inhibits necrosis in the human myocardium by signal transduction pathways that involve mitoKATP channels, PKC and p38MAPK. However, apoptosis that is inhibited by activation of mitoKATP channels and PKC is p38MAPK-independent. The observed changes in gene expression may help to understand the pathophysiology of ischaemic/reoxygenation injury and the mechanism of cardioprotection. With the information obtained in this thesis we have gained more information on the role of apoptosis in ischaemia/reperfusion injury of the human myocardium and a greater understanding of the underlying mechanisms and the signal transduction of cardioprotection by IPC. It is hoped that this knowledge will contribute to the design of therapeutical strategies that may reduce myocardial ischaeia/reperfusion injury in man..
Type: Thesis
Level: Doctoral
Qualification: MD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Cardiovascular Sciences
Leicester Theses

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