Bullard, A.J.;
(2006)
The role of erythropoietin in ischaemia/reperfusion injury.
Doctoral thesis , University of London.
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Abstract
Background - Ischaemia/reperfusion accounts for a large proportion of fatalities in the developed world. Even if death is avoided, the patient suffers a deterioration in their quality of life. Erytriropoietin (EPO) has been examined in clinical studies investigating its effect in anaemic chronic heart failure patients with any positive effect attributed to the correction of anaemia. Given the recent discovery of the EPO receptor on the myocyte surface, this thesis examined whether EPO could have a direct effect on the myocardium and limit ischaeinia/reperfUsion injury and the mechanism by which any protection occurs. Methods and results - Using an isolated perfused rat model of ischaemia/reperfusion, we demonstrated that EPO could mimic preconditioning in a P1-3-Kinase (PI3K)- dependent manner. Adrninistration of EPO at reperfusion limited infarct size by activation eNOS and could be abolished by inhibitors of NOS, PI3K and ERK 1/2. This thesis also showed that EPO could delay mitochondrial permeability transition pore opening (mPTP) in an oxidative stress myocyte model of mPTP opening, an effect that was suppressed by inhibitors of NOS and PBK. A 3 week treatment of EPO reduced injury in a NOS-dependent manner that was independent of haematocrit. Finally this thesis demonstrated that administration of EPO as late as 30 minutes after commencement of reperfusion could still reduce infarct size. Conclusion - This thesis demonstrated that EPO can be used in a variety of settings to elicit a protective effect against ischaemia/reperfusion injury. This variety of effective time points promises an important future role for EPO in the treatment of ischaemic heart disease.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The role of erythropoietin in ischaemia/reperfusion injury. |
| Identifier: | PQ ETD:592652 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by Proquest |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1445332 |
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