Effects of sex hormones on ECG parameters and expression of cardiac ion channels in dogs

Aim: The aim of the study was to examine the effects of testosterone and oestrogen on the ECG parameters and expression of cardiac ion channels in male and female dogs, and to compare the dofetilide-induced lengthening of QTc interval in control, castrated and hormone-treated animals. Methods: ECG records were taken from male and female anaesthetized dogs (n = 10 in each group) before castration, after castration, and following inverted hormone substitution. The animals were challenged with dofetilide at each stage of the experiment. Finally, the hearts were excised and expression of ion channels was studied using Western blot technique. Results: Heart rate was decreased and PQ interval increased by deprivation of sex hormones in both genders (orchiectomy or ovarectomy), while inverted hormonal substitution restored control values. Orchiectomy significantly increased the duration of QT and QTc intervals, QTc-dispersion and the dofetilide-induced lengthening of QTc, while testosterone treatment of castrated females had opposite effects. Intraventricular conduction (QRS duration) was independent of the endocrine status of the animals. Ovarectomy or oestrogen treatment of castrated males failed to alter significantly these parameters except for QTc-dispersion. Expression of ion channel proteins responsible for mediation of I-K1 and I-to currents (Kir2.1 and Kv4.3, respectively), was significantly higher in the testosterone-treated castrated females and normal males than in the oestrogen-treated castrated males and normal females. Conclusion: Repolarization of canine ventricular myocardium is significantly modified by testosterone, but not oestrogen, in both genders. This effect is likely due to augmentation of expression of K+-channel proteins, and thus may provide protection against arrhythmias via increasing the repolarization reserve.