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Using a mouse model of myocardial infarction (MI), we studied the dose\u2010effect of oestrogen replacement on mortality and cardiac remodelling and dysfunction post\u2010MI in the absence of progestin. Six\u2010week\u2010old females were subjected to ovariectomy (OVX). A pellet containing a low, moderate or high dose of 17\u03b2\u2010oestradiol (E<jats:sub>2<\/jats:sub>; 0.42, 4.2 or 18.8 \u03bcg day<jats:sup>\u22121<\/jats:sup>) or placebo was implanted subcutaneously on the day of OVX. Myocardial infarction was induced 8 weeks later, and cardiac morphology and function were evaluated 8 weeks after MI. We found that E<jats:sub>2<\/jats:sub> at moderate and high doses adversely affected mortality. A low dose of E<jats:sub>2<\/jats:sub> that restored plasma oestrogen close to physiological levels had no significant effect on mortality but tended to improve cardiac function and remodelling, associated with reduced fibrosis and increased capillary density. At the moderate dose, E<jats:sub>2<\/jats:sub> exacerbated cardiac fibrosis, hypertrophy, dysfunction and dilatation, associated with liver and kidney enlargement and ascites. Protein kinase C and extracellular signal\u2010regulated kinase were increased by MI but were not affected by E<jats:sub>2<\/jats:sub>. In summary, E<jats:sub>2<\/jats:sub> at a low dose tended to be cardioprotective. At increased doses that raised plasma oestrogen far beyond the physiological level, E<jats:sub>2<\/jats:sub> was detrimental to the heart. Our data suggest that dosage should be an important consideration when studying the effect of oestrogen replacement on the heart.<\/jats:p>","DOI":"10.1113\/expphysiol.2008.042788","type":"journal-article","created":{"date-parts":[[2008,5,17]],"date-time":"2008-05-17T00:45:07Z","timestamp":1210985107000},"page":"982-993","source":"Crossref","is-referenced-by-count":26,"title":["Dose\u2010dependent cardiac effect of oestrogen replacement in mice post\u2010myocardial 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