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Title: Oestrogen and the post-myocardial infarction heart : benefit or detriment?
Author: Jeanes, Helen L.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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This thesis aimed firstly to investigate the effects of oestrogen (E) on the myocardium during healing after MI. In ovariectomised female mice, E treatment results in an increase in acute mortality due to cardiac rupture following induction of MI by coronary artery ligation. E disrupts matrix degradation during infarct healing after MI. In the mouse this results in an increased incidence of cardiac rupture. A second aim of the thesis was to determine the roles of the E receptor (ER) α and ERβ in mediating the initial cardioprotective effects of E following MI. E reduced infarct size, neutrophil infiltration and generation of oxidant stress following myocardial ischaemia with reperfusion in rats. This effect was not blocked by a novel ERβ antagonist but was mimicked by a novel ERα agonist. The ERα agonist also protected the isolated buffer perfused heart from reperfusion injury showing that it has both neutrophil dependent and independent effects. A third aim of the thesis was to determine whether inclusion of a progesterone analogue in hormone replacement therapy (HRT) regimes modifies the cardioprotective effects of E. In ovariectomised female rats, E supplementation reduced infarct size and neutrophil infiltration following ischaemia and reperfusion compared to placebo treated animals. This protection was lost in animals receiving the progesterone analogue medroxyprogesterone acetate (MPA) in addition to E. Co-administration of MPA therefore negates the beneficial effects of E in myocardial reperfusion injury. In conclusion, the data confirm the initial cardioprotective effects of E following myocardial infarction with or without reperfusion. At least in the rate, this protection is mediated through stimulation of the ERα, through direct effects on the heart and additional effects on neutrophils. This protective influence of E is lost if E is co-administered with MPA, as it frequently is in HRT regimes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available