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Repolarization Reserve (repolarization + reserve)
Selected AbstractsSlow Delayed Rectifier Potassium Current (IKs) and the Repolarization ReserveANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2007Norbert Jost Ph.D. The aim of this review is to present the properties of the slow component of the delayed rectifier potassium current (IKs) in the human ventricle. The review gives a detailed description of the physiology, molecular biology and pharmacology of the IKs current, including kinetic properties, genetic structures, agonists and antagonists. The authors also present the role of the IKs current in the human cardiac repolarization focusing on several pathophysiological situations, such as the LQT syndrome and the Torsade de Pointes arrhythmia. [source] Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and humanFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2006Jianhua Cheng Abstract Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K+ currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization. [source] Proarrhythmia as a Class Effect of Quinolones: Increased Dispersion of Repolarization and Triangulation of Action Potential Predict Torsades de PointesJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2007PETER MILBERG M.D. Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via IKr blockade in an intact heart model of proarrhythmia. Methods and Results: In 47 Langendorff-perfused, AV-blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 ,M to 1,000 ,M were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse-use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP. Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP. [source] Modelling and imaging cardiac repolarization abnormalitiesJOURNAL OF INTERNAL MEDICINE, Issue 1 2006Y. RUDY Abstract. Repolarization abnormalities, including those induced by the congenital or acquired long QT (LQT) syndrome, provide a substrate for life-threatening cardiac arrhythmias. In this article, we use computational biology to link HERG mutations mechanistically to the resulting abnormalities of the whole-cell action potential. We study how the kinetic properties of IKs (the slow delayed rectifier) that are conferred by molecular subunit interactions, facilitate its role in repolarization and ,repolarization reserve'. A new noninvasive imaging modality (electrocardiographic imaging) is shown to image cardiac repolarization on the epicardial surface, suggesting its possible role in risk stratification, diagnosis and treatment of LQT syndrome. [source] | ||||||||||