Background and purpose: Female sex hormones may protect pre-menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17b-estradiol, on ischaemia-induced cardiac arrhythmias and on the L-type Ca 2 þ current (I CaL ). Experimental approach: In vivo experiments were performed in pentobarbital-anaesthetized rats subjected to acute coronary artery occlusion. I CaL was measured by the whole-cell patch-clamp technique, in rat isolated ventricular myocytes. Key results: Acute intravenous administration of 17b-estradiol as a bolus dose followed by a continuous infusion, commencing 10 min before coronary artery occlusion, had dose-dependent antiarrhythmic activity. In female rats 300 ng kg -1 þ 30 ng kg À1 min À1 17b-estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17b-estradiol was required to cause similar effects in male rats. In vitro 17b-estradiol reduced peak I CaL in a concentration-dependent manner. The EC 50 was ten-fold higher in male myocytes (0.66 mM) than in females (0.06 mM). Conclusions and implications:These results indicate that 17b-estradiol has marked dose-dependent antiarrhythmic activity that is greater in female rats than in males. A similar differential potency in blocking I CaL in myocytes from female and male rats can account for this effect. This provides an explanation for the antiarrhythmic activity of 17b-estradiol and gender-selective protection against sudden cardiac death.

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