Female Gender is a Risk Factor for Drug‐Induced Long QT and Cardiac Arrhythmias in an In Vivo Rabbit Model

作者：Hua Rong Lu, Paul Remeysen, KATRIEN SOMERS, AN SAELS, Fred De Clerck · 发表于：Journal of Cardiovascular Electrophysiology · 年份：2001 · 被引用次数：79 · 研究领域：Cardiac electrophysiology and arrhythmias、Takotsubo Cardiomyopathy and Associated Phenomena、ECG Monitoring and Analysis

INTRODUCTION: Clinical observations and in vitro experimental data indicate that females have a longer QT interval than males, which is associated with a higher risk of drug-induced cardiac arrhythmias. Little is known about this gender difference in anesthetized animals, which may affect the outcome of in vivo drug tests. METHODS AND RESULTS: We evaluated potential gender differences in ventricular repolarization (QT, QTc, JT, and JTc interval) and its dispersion, as well as in its response to dofetilide, an IKr blocker, in anesthetized rabbits challenged with the alpha1-adrenoceptor agonist methoxamine. A 12-lead ECG was recorded during the experiments. At baseline, there were no significant gender differences in ventricular repolarization values in male and female rabbits under anesthesia. Dofetilide (0.04 mg/kg/min IV for 60 min; n = 10 per gender) produced marked prolongation of the ventricular repolarization time and its dispersion, associated with a high incidence of polymorphic ventricular tachycardia (PVT; 100% in females vs 80% in males) and ventricular fibrillation (VF; 80% in females vs 50% in males; P > 0.05). QT and JT interval at 2 minutes as well as QT and JT dispersion at 10 and 30 minutes during dofetilide infusion were significantly higher in female than in male rabbits. After 30 minutes of dofetilide infusion, 10 of 10 female rabbits had severe cardiac arrhythmias (complete AV block, PVT, or VF), so ECG parameters were impossible to assess (vs 3/10 males w...