sodium-ethylxanthate and Long-QT-Syndrome

There is increased awareness of the impact of gender and gonadal steroids on human cardiac rhythm and arrhythmias; e.g., drugs that prolong repolarization induce torsades de pointes (TdP) more frequently in women than men; female gender is an independent risk factor for syncope and sudden death in the congenital long QT syndrome; and the higher propensity toward arrhythmia in normal females is associated with fundamental differences in repolarization such that rate-corrected QT intervals are longer in females than males. Mechanisms underlying these differences are incompletely defined but are believed to involve gonadal steroids. This review discusses recent advances and prospects for further elucidation of the influence of gender and gonadal steroids on ventricular repolarization and arrhythmias.

Topics: Aging; Animals; Arrhythmias, Cardiac; Electrocardiography; Electrophysiology; Female; Gonadal Steroid Hormones; Humans; Ion Channels; Long QT Syndrome; Male; Myocardium; Phenethylamines; Potassium Channel Blockers; Rabbits; Receptors, Androgen; Receptors, Estrogen; Sex; Sulfonamides

Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to beta-adrenoceptor blockade.. 12-lead ECGs before and during beta-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals.. (1) Adult males had the greatest shortening of the QTc interval upon treatment with beta-adrenoceptor blockade. During treatment, adult males with LQTS(1) (mutation in the KCNQ1 gene, affecting I(Ks) current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS(2) patients (mutation in the HERG gene, affecting I(Kr) current). (2) Female LQTS(2) patients had a 50% larger dispersion than female LQTS(1) patients both before and during treatment. (3) Adult male LQTS(1) patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to beta-adrenoceptor blockade.. These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to beta-adrenoceptor blockade can be modulated by gender-related factors.

Topics: Adrenergic beta-Antagonists; Adult; Analysis of Variance; Child; Electrocardiography; Female; Genotype; Humans; KCNQ Potassium Channels; KCNQ1 Potassium Channel; Long QT Syndrome; Male; Mutation; Mutation, Missense; Potassium Channels; Potassium Channels, Voltage-Gated; Sex