Sematilide prolonged action potential duration and effective refractory period in guinea pig atrium, proving approximately 20 times more potent than sotalol on a molecular basis.
Does sematilide prolong action potential duration and effective refractory period compared to sotalol in guinea pig atrium?
Sematilide is a potent class III antiarrhythmic agent that prolongs action potential duration and effective refractory period in guinea pig atrium without reverse rate-dependence, suggesting potential efficacy for atrial arrhythmias.
Electrophysiological effects of sematilide, a novel class III antiarrhythmic agent, were examined and compared with those of (+/-)sotalol in guinea pig left atrium by a conventional microelectrode technique. Application of 0.1-1000 microM sematilide or 1-1000 microM (+/-)sotalol concentration-dependently prolonged the duration of action potentials (APD) that were elicited by electrical stimulation at 1 Hz. Other parameters of action potentials such as the maximum upstroke velocity of phase 0 depolarization, action potential amplitude and resting membrane potential were not affected significantly by these drugs in the concentration ranges employed. The prolongation of APD by sematilide or (+/-)sotalol was accompanied by a corresponding increase in the effective refractory period (ERP). Approximately a 30% increase in ERP was obtained by the treatment with 5 microM sematilide or 100 microM (+/-)sotalol, suggesting that sematilide as a class III antiarrhythmic agent is approximately 20 times more potent than (+/-)sotalol on a molecular basis. When the stimulation rate was increased stepwise from 0.2 to 2 Hz, the relative increase in APD at 90% repolarization by the treatment with sematilide and (+/-)sotalol was slightly larger at 2 Hz than at 0.2 Hz, indicating that "reverse rate-dependence" was not observed under these conditions. These results may suggest a possibility that sematilide effectively blocks atrial arrhythmia.
Ishii et al. (Sun,) conducted a other in Atrial arrhythmia. Sematilide vs. (+/-)sotalol was evaluated on Duration of action potentials (APD) and effective refractory period (ERP). Sematilide prolonged action potential duration and effective refractory period in guinea pig atrium, proving approximately 20 times more potent than sotalol on a molecular basis.