Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats.

摘要

BACKGROUND: Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. METHODS: Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17beta-oestradiol (E2) supplements (10 mug, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). RESULTS: In oophorectomised rats plasma levels of E2 declined from 1301 +/- 80 to 196 +/- 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by approximately 60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 +/- 2.0 to 6.0 +/- 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 +/- 1.2% to 18.1 +/- 2.3%, p<0.05), increased SBP (from 82 +/- 4.2 to 97 +/- 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. CONCLUSION: Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved.