| Objective:To investigate the physiological changes of cardiac repolarization in females during menstreal cycle and their underlying mechanisms,the modification of female hormones on the repolarization and the susceptibility to the classⅢantiarrhythmic agents induced arrhythmias were studied in rabbits by ovariectomy and hormone replacement therapy(HRT).This may have implications for the development of the safest medicinal products and for the reduction of drug-induced arrhythmias.Methods:1.Human ECG recordings:Thirty-nine healthy female volunteers aged 18-22 years old with regular menstrual cycles of 28-30 days were enrolled in the study.The 12-lead ECG was recorded three times(named as A,B and C respectively)during menstrual cycles,A was performed within 24 hours before or after the onset of menses,B and C were performed at day 16 or 17 and day 7 or 8 from the last of the menstrual cycle,respectively.RR,QTp,QT,JTp,JTe and QT dispersion were measured for analysis.2.Animal ECG recordings:45 ovariectomized rabbits were randomly divided into three groups:control group(NS),estradiol group(E),estradiol plus progesterone group(E+P).One week after ovariectomy,they were treated with different hormones or placebo for two weeks.The doses of the drugs used were: normal saline 1 ml/kg/d in NS group,estradiol 100μg/kg/d in E group,estradiol 100μg/kg/d plus progesterone 5 mg/kg/d in E+P group.All of them were injected intramuscularly.Limb-lead ECG was recorded three times for each animals:before ovariectomy,one week after ovariectomy,after two weeks HRT.RR,QTp,QT,JTp, JTe and QT dispersion of leadⅡwere measured for analysis.After that,sotalol was injected intravenously at a speed of 1 mg/kg/min with a total dose of 20 mg/kg.ECG was monitored and recorded during the injection and within 30 min after the injection. The rate of sotalol induced arrhythmias and the mortality as well as the dose of sotalol for the initial arrhythmias were analysized in each group.Results:The cardiac repolarization of the females had some physiologyical changes during the menstrual cycle.The parameters of ECG(not rectified)in B was longer than A,among them QTp and QT had a significant meaning(P＜0.05,n=45). There was no obvious difference between A and C.The parameters of ECG in ovariectomized rabbits were significantly shorter than the intact animals(except JTp) (P＜0.05,n=45).After two weeks treatment with hormones the ECG parameters of E group were all slightly prolonged compared with the NS group,but had no significant difference(P＞0.05,n=15).The parameters of ECG in E+P group were significantly shorter than E group(P＜0.05,n=15),whereas similar to the NS group. The rate of sotalol hydrochoride induced arrhythmias during the injection and the mortality in E group was significant higher than NS and E+P groups,and the dose of sotalol for the initiation of arrhythmias in E group was significantly lower than NS and E+P groups.Conclusions:The physiological changes of cardiac repolarization has relation to the females menstreal cycle.Estradiol can reduce the repolarization reserve and thus increase the susceptibility of sotalol induced arrhythmias.Whereas progesterone may shorten the repolarization and decrease the dispersion of repolarization,thus protects the females from drug-induced arrhythmias. |
