Effects of the antiarrhythmic agent tedisamil on cardiac potassium currents in humans (part 11). DISCUSSION

28 Aug
2012

 Tedisamil converts the noninactivating Iso into an inactivating current, and the contribution of Iso to final repolarization should thereby be considerably reduced. From this point of view, tedisamil may have a greater potential as an antiarrhythmic drug in the treatment of atrial fibrillation than of ventricular arrhythmias. The pronounced use-dependency of tedisamil action is an advantage for a class Ill agent. However, the rather slow time course for recovery from block makes it unlikely that the drug effect is substantially modulated within physiological or pathophysiological ranges of heart rates. An open channel block of Ito and Iso is found not only with tedisamil but also with clofilium and quinidine (unpublished data).Our results were obtained at room temperature; however, the kinetics of tedisamil block and unblock may be substantially different at physiological temperature. Furthermore, the tedisamil effects obtained in human subepicardial ventricular and in atrial myocytes may not be representative of the whole heart. In human papillary muscles, prolongation in action potential duration by tedisamil 1 |J,M was fully developed after long periods of rest . This effect does not suggest an open channel block, but could be compatible with a closed channel block or a fast open channel block with trapping of the substance , although action potential data alone cannot prove this. As in guinea pig myocytes, tedisamil may predominantly affect delayed rectifier currents such as Iks and Ikt in human papillary muscles , although it must be mentioned that we were not able to detect Iks and Ik in human atrial or ventricular myocytes. Nevertheless, others have occasionally reported delayed rectifier currents in human ventricular and atrial myocytes . In addition to blocking of potassium currents (with the exception of Iki ), tedisamil inhibits sodium current, albeit only at concentrations above 20 |JM. L-type calcium current, on the other hand, is not influenced by concentrations up to 50 |JM. Find best deals an online pharmacy can offer and get a chance to start your treatment soon. You can now purchase cheap kamagra online cialis professional 20 mg at the best pharmacy that will be sure to live up to your expectations every single time.

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