The effects of D-sotalol on the spontaneous sinus rate have been attributed not to calcium antagonistic efficacy, but to prolongation of the pacemaker cell action potential duration . The more marked negative chronotropic action of tedisamil would suggest that there was an additional effect on the calcium-dependent pacemaker currents, but an only minor influence on AV nodal refractoriness did not support this. A lack of effects on the calcium currents was also described by Dukes and Morad and by Adaikan et al . The slight effects of sotalol and tedisamil on the AV node may therefore only be explainable by a minor prolongation of the action potential in the AV node region. One remarkable difference between tedisamil and D-sotalol is the prolongation of His bundle and intraventricular conduction and the marked prolongation of atrial myocardial refractoriness by high concentrations of tedisamil. These findings indicate a direct effect of tedisamil on the sodium currents of the myocardium, which is in agreement with the data of Dukes and Morad and of Abraham et al . A further difference between the drugs was found to be a significantly higher prolongation of the JT interval by tedisamil, indicating a more potent effect on the potassium channels.For all class III antiarrhythmic compounds, a reverse use-dependent effect has been described, ie, their ability to prolong repolarization was diminished at increased heart rates and enhanced by bradycardia . This is also described for tedisamil and D-sotalol, but effects of tedisamil on action potential duration were diminished, but not cancelled, by higher stimulation rates . In our experiments at high concentrations (10 |jM) both drugs induced a slight prolongation of the V-ERP. This effect decreased with the increase in stimulation rate under the influence of D-sotalol (240 ms S1-S1: +18 ms; 200 ms S1-S1: +17 ms; 180 ms S1-S1: + 10 ms), whereas it slightly increased under the influence of tedisamil (240 ms S1-S1: +13 ms; 200 ms S1-S1: +15 ms; 180 ms S1-S1: +21 ms). The reason for this different efficacy may be the additional sodium antagonistic effect of tedisamil at high concentrations. As shown for other antiarrhythmic compounds with combined class I and class III effects, such as amiodarone, the reverse use-dependent effect was attenuated when an additional sodium antagonistic effect was present. You will always be glad to find Advair Diskus for Asthma buy here and enjoy your online shopping.