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101.
Sandri M Adams V Gielen S Linke A Lenk K Kränkel N Lenz D Erbs S Scheinert D Mohr FW Schuler G Hambrecht R 《Circulation》2005,111(25):3391-3399
102.
103.
Effect of amiodarone on the plasma levels of metoprolol 总被引:4,自引:0,他引:4
Werner D Wuttke H Fromm MF Schaefer S Eschenhagen T Brune K Daniel WG Werner U 《The American journal of cardiology》2004,94(10):1319-1321
On average, metoprolol plasma concentration is doubled after an amiodarone loading dose (1.2 g/day over a period of 6 days). However, the individual amount of this drug interaction depends on the CYP2D6 genotype. 相似文献
104.
Human hereditary long QT syndrome is a cardiac disease characterized by prolongation of the QT interval and increased susceptibility to ventricular arrhythmias and sudden cardiac death. Mutations in the human-ether-a-go-go-related gene (hERG), encoding the protein underlying the repolarizing cardiac I(Kr) potassium current, cause chromosome 7-linked long QT syndrome 2. Loss of function of mutant hERG channels may be caused by several mechanisms, including altered current kinetics, altered ion selectivity, or defective intracellular protein trafficking. Especially the latter category has become a focus of particular interest recently, because some of the mutant subunits display wild type current properties when normal trafficking is restored and channels are inserted in the cell membrane in vitro. This review summarizes the current knowledge on hERG channel trafficking under physiological and pathological conditions. In addition, therapeutic approaches to restore normal hERG trafficking in vitro and in vivo are discussed. 相似文献
105.
Acute effects of dronedarone on both components of the cardiac delayed rectifier K+ current, HERG and KvLQT1/minK potassium channels 总被引:3,自引:0,他引:3
Thomas D Kathofer S Zhang W Wu K Wimmer AB Zitron E Kreye VA Katus HA Schoels W Karle CA Kiehn J 《British journal of pharmacology》2003,140(5):996-1002
Dronedarone is a noniodinated benzofuran derivative that has been synthesized to overcome the limiting iodine-associated adverse effects of the potent antiarrhythmic drug amiodarone. In this study, the acute electrophysiological effects of dronedarone on repolarizing potassium channels were investigated to determine the class III antiarrhythmic action of this compound. HERG and KvLQT1/minK potassium channels conduct the delayed rectifier potassium current IK in human heart, being a primary target for class III antiarrhythmic therapy. HERG and KvLQT1/minK were expressed heterologously in Xenopus laevis oocytes, and the respective potassium currents were recorded using the two-microelectrode voltage-clamp technique. Dronedarone blocked HERG channels with an IC50 value of 9.2 microM and a maximum tail current reduction of 85.2%. HERG channels were blocked in the closed, open, and inactivated states. The half-maximal activation voltage was shifted by -6.1 mV, and HERG current block by dronedarone was voltage-dependent, but not use-dependent. Dronedarone exhibited a weaker block of KvLQT1/minK currents (33.2% at 100 microM drug concentration), without causing significant changes in the corresponding current-voltage relationships. In conclusion, these data demonstrate that dronedarone is an antagonist of cloned HERG potassium channels, with additional inhibitory effects on KvLQT1/minK currents at higher drug concentrations, providing a molecular mechanism for the class III antiarrhythmic action of the drug. 相似文献
106.
Kathöfer S Röckl K Zhang W Thomas D Katus H Kiehn J Kreye V Schoels W Karle C 《Naunyn-Schmiedeberg's archives of pharmacology》2003,368(2):119-126
Modulation of the slow component of the delayed rectifier potassium current (IKs) in heart critically affects cardiac arrhythmogenesis. Its current amplitude is regulated by the sympathetic nervous system. However, the signal transduction from the -adrenergic system to the KvLQT1/MinK (KCNQ1/KCNE1) potassium channel, which is the molecular correlate of the IKs current in human cardiomyocytes, is not sufficiently understood. In the human heart, three subtypes of -adrenergic receptors (1–3-ARs) have been identified. Only 1- and 3-ARs have been shown so far to be involved in the regulation of IKs. Special interest has been paid to the regulation of IKs by the 3-AR because of its potential importance in congestive heart failure. In heart failure 1-ARs are known to be down regulated while the density of 3-ARs is increased. Unfortunately, studies on the modulation of IKs by 3-AR revealed conflicting results. We investigated the functional role of protein kinase C (PKC) in the signal transduction cascade between 3-adrenergic receptors and IKs by expressing heterologously its molecular components, the KvLQT1/MinK potassium channel, together with human 3-AR in Xenopus oocytes. Membrane currents were measured with the double electrode voltage-clamp technique. Using activators and inhibitors of PKC we demonstrated that PKC is involved in this regulatory process. Experiments in which the putative C-terminal PKC-phosphorylation sites in the KvLQT1 protein were destroyed by site directed mutagenesis reduced the isoproterenol-induced current to 27±3,5% compared to control. These results indicate that the amplitude of KvLQT1/MinK current is mainly increased by PKC activation. Our results suggest that the regulation of the KvLQT1/MinK potassium channel via 3-AR is substantially mediated by PKC phosphorylation of the KvLQT1 protein at its four C-terminal PKC phosphorylation sites.S. Kathöfer, K. Röckl and W. Zhang contributed equally to this paper 相似文献
107.
Dierk Vorwerk M.D. Rolf W. Günther Klaus Bohndorf Peter Keulers 《Cardiovascular and interventional radiology》1991,14(5):316-319
In 2 patients, an aortic stenosis failed to respond adequately to balloon dilatation but was successfully treated by implantation
of a self-expandable large caliber endoprosthesis and subsequent balloon angioplasty. Intravascular ultrasound helped to classify
the characteristics of the lesion in preparation for intervention. 相似文献
108.
BRL-32872 is a new antiarrhythmic drug with balanced class-III and class-IV actions as categorized by the Vaughan-Williams classification. BRL-32872 blocks the rapid component of the cardiac delayed rectifier potassium channel IK(r) (IC(50) = 28 nM) and its molecular correlate HERG ("Human-ether-a-go-go related gene," IC(50) of 19.8 nM in cell lines) at low concentrations. It also inhibits the L-type calcium current (ICa) at higher concentrations (IC(50) = 2.8 microM). This dual concentration-dependent profile of action at higher concentrations may possibly prevent "torsades de pointes" ventricular arrhythmias, which is a dangerous side effect of many other class-III antiarrhythmic drugs. With BRL-32872, an excessive prolongation of the action potential duration and consecutive QTc prolongation is prevented by a concentration-dependent increase of calcium channel block, resulting in the so-called "bell-shaped" profile of antiarrhythmic drug action. BRL-32872 is very effective in the treatment of ventricular arrhythmias in animal models of cardiac ischemia. In the ischemic hearts of animals the drug significantly reduced early afterdepolarization and ventricular tachycardia. The antiarrhythmic effect of BRL-32872 has not yet been demonstrated in humans. 相似文献
109.
Water jet discotomy with microinvasive approach--in vitro testing and initial clinical aspects of a new procedure 总被引:2,自引:0,他引:2
Honl M Dierk O Küster JR Müller G Müller V Hille E Morlock M 《Zeitschrift für Orthop?die und ihre Grenzgebiete》2001,139(1):45-51
AIM: The difference in consistence of the nucleus pulposus and the annulus fibrosus allows the water jet to selectively remove the nucleus in a closed vertebral disc at a certain pressure range. The aim of the study was to investigate the use of water jet cutting in microinvasive spinal surgery. METHODS: A comparison in terms of efficiency between the water jet and those of the laser and APLD (automatic percutaneous lumbar discotomy) was achieved by plastic reconstruction of the resected spaces using the in-vitro-model of the spinal column of young pigs. The in-vitro-study was followed by a prospective clinical study with 21 patients. RESULTS: The in-vitro-employment of the three different methods showed that there were no significant differences in volume of the removed nucleus material. During the use of the hydro jet at 50 bar and simultaneous suction the intradiscal pressure measured in vitro remained below 1 bar. Clinical tests on the 21 patients showed good to very good results in 71% of the patients tested (mean follow-up 5.8 months). No complications were found. As working mechanism the pure mechanical effect and the influence on chemical processes within the nucleus remain points for discussion. CONCLUSION: The current studies results demonstrate that hydrojet spinal surgery might be a safe new method for surgery of disc protrusion and contained prolapse. 相似文献