Effects of Gonadal Steroids on Ventricular Repolarization and on the Response to E40311
- Departments of 1Pharmacology (M.H., P.D.Jr., M.R.R.) and 2Pediatrics (M.R.R.), Partnership for Women’s Health, College of Physicians and Surgeons of Columbia University, New York, New York
Abstract
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.
Footnotes
-
Send reprint requests to: Michael R. Rosen, M.D., Gustavus A. Pfeiffer Professor of Pharmacology, Professor of Pediatrics, College of Physicians and Surgeons of Columbia University, Department of Pharmacology, 630 West 168 Street, PH 7West-321, New York, NY 10032. E-mail: franeye{at}cudept.cis.columbia.edu
-
↵1 This work was supported by U.S. Public Health Service, National Heart, Lung, and Blood Institute Grant HL28958 and by Procter and Gamble.
- Abbreviations:
- AP
- action potential
- DHT
- dihydrotestosterone
- MDP
- maximum diastolic potential
- V˙max
- maximum rate of rise of phase 0 of the action potential
- APD30
- action potential duration to 30% repolarization
- APD50
- action potential duration to 50% repolarization
- APD90
- action potential duration to 90% repolarization
- EAD
- early afterdepolarization
- CL
- cycle length
-
- Received September 9, 1997.
- Accepted February 13, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
