Effects of gonadal steroids on ventricular repolarization and on the response to E4031

Gonadal steroids are thought to be important determinants of gender-related differences in electrophysiology, such as the longer rate-corrected QTc intervals in women and the incidences of some clinical arrhythmias. We studied the chronic effects of gonadal steroids on cardiac action potentials (APs) using standard electrophysiological techniques. Papillary muscles were removed from the hearts of oophorectomized rabbits that had been treated with placebo, estradiol or dihydrotestosterone (DHT). The electrocardiograms of the three groups did not differ. Papillary muscle APs were studied during drive at cycle lengths of 330 to 5000 msec. The APD30 of the DHT group was significantly shorter than that of the others at cycle lengths of >500 msec. The APD90 of the estradiol group was significantly longer than that of the DHT group at cycle lengths of >1000 msec. The APD90 of the placebo group tended to be intermediate. The effects of the antiarrhythmic drug E4031 (10(-8)-10(-6) M) also were examined. E4031-induced prolongation of APD90 and magnitude of early afterdepolarizations was significantly greater in the estradiol-treated than the DHT-treated and placebo groups. In conclusion, in rabbit heart, gonadal steroids are important determinants of base-line electrophysiological properties and the proarrhythmic response to E4031.