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摘要
This study aimed to comparatively investigate the acute modulating effects of oestrogen and progesterone on the repolarization and the susceptibility of female rabbits to class III anti-arrhythmic agents. The acute influence of estradiol and progesterone on the cardiac repolarization and the drug sensitivity of the rapidly activating delayed rectifier K+ channel to sotalol was comparatively studied in Langendorff-perfused rabbit hearts at pharmacological concentrations through recording of epicardial monophasic action potentials. In Langendorff-perfused rabbit hearts, estradiol (130 mu m) concentration-dependently prolonged the monophasic action potential durations (MAPD30 and MAPD90) (P < 0.05); while the effects of progesterone on MAPD were biphasic: it prolonged MAPD30 and MAPD90 at lower concentrations (13 mu m) but shortened MAPD30 and MAPD90 at higher concentrations (1030 mu m). Sotalol-induced prolongation of MAPD90 was significantly less in the hearts pretreated with progesterone than those treated with estradiol (P < 0.05). The incidence of the pro-arrhythmic events induced by sotalol in the hearts pretreated with progesterone was also significantly lower than those pretreated with estradiol (P < 0.05). In conclusion, estradiol and progesterone have different modulating effects on cardiac repolarization: estradiol can concentration-dependently prolong the cardiac repolarization time and thus may reduce the repolarization reserve and increase the susceptibility of female rabbits to sotalol-induced arrhythmias, whereas progesterone may shorten the cardiac repolarization time at concentrations above 10 mu m, thus protecting the heart from drug-induced arrhythmias.
- 出版日期2012-4
- 单位同济大学
