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Vol. 285, Issue 3, 1068-1072, June 1998
Departments of
Pharmacology (M.H., P.D.Jr., M.R.R.) and
Pediatrics
(M.R.R.), Partnership for Women's Health, College of Physicians and
Surgeons of Columbia University, New York, New York
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
8-106 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.
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