Diverse modulating effects of estradiol and progesterone on the monophasic action potential duration in Langendorff-perfused female rabbit hearts

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.