title: Concurrent supplement of estradiol and progesterone reduces the cardiac sensitivity to D,L-sotalol-induced arrhythmias in ovariectomized rabbits.
abstract: BACKGROUND
  Although the difference in the modulation of estradiol and dihydrotesterone on ventricular repolarization has been intensively studied, little information is available concerning the role of the different ovarian hormones in the modulation of repolarization in the female.
  
  
  METHODS
  The chronic modulation of female hormones, estradiol, and progesterone, on cardiac repolarization and the susceptibility to d,l-sotalol, a class III antiarrhythmic agent, were studied in female rabbits by ovariectomy and hormone replacement therapy (HRT) through recording and analyzing of electrocardiograms.
  
  
  RESULTS
  The corrected QT interval (QTc) measured 2 weeks after ovariectomy was not significantly different from that in the time-matched control rabbits. After 2 weeks of HRT, the QTc in the ovariectomized rabbits treated with estradiol alone (group E) was not significantly different from that in the control (group C); whereas in the ovariectomized rabbits treated with estradiol plus progesterone (group E + P), it was significantly shorter than those in groups E (P < .05) and C (P < .01), respectively. The corrected Tpeak-end interval (Tpec), an indicator of global dispersion of ventricular repolarization, was also significantly reduced in group E + P compared with that of group C (P < .01). In group E, d,l-sotalol-induced prolongation of QTc and the rate and the severity of arrhythmias were significantly higher, while the dose of sotalol to initiate arrhythmias was significantly lower than those in groups C or E + P, respectively (P < .05 or P < .01).
  
  
  CONCLUSIONS
  Estradiol potentiates QTc prolonging effects of d,l-sotalol and increases the susceptibility to d,l-sotalol-induced arrhythmias without significantly altering QTc itself, whereas progesterone may accelerate the process of repolarization and protect the females from drug-induced arrhythmias, thus counteracting the effect of estradiol.
authors.affiliation: Department of Pharmacology, School of Medicine, Tongji University, Shanghai, China. jcheng@tongji.edu.cn
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cheng
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.forename: Hanyi
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D012720:Severity of Illness Index; D013015:Sotalol / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D011374:Progesterone; D004958:Estradiol; D013015:Sotalol