caa a22 4500 477072593 CHVBK 20180405111430.0 cr unu---uuuuu 170330e19961101xx s 000 0 eng 10.1007/BF00050994 doi (NATIONALLICENCE)springer-10.1007/BF00050994 Assessment of frequency dependency of the class III effects of almokalant: A study using programmed stimulation and recording of monophasic action potentials and ventricular paced QT intervals [Elektronische Daten] [Börje Darpö, Olle Almgren, Robert Bergstrand, Stefan Franzén, Nils Edvardsson] Summary: The aim of the present study was to assess the frequency dependency of the effects of almokalant, a selective class III antiarrhythmic drug, on ventricular repolarization using recordings of monophasic action potentials and measurements of ventricular paced QT intervals. Twenty male volunteers were studied during almokalant infusion aiming at plasma concentrations (Cpl) of 20, 50, 100, and 150 nmol/l. The duration of monophasic action potential at 90% repolarization (MAPD) was measured during incremental and premature ventricular extrastimulation. The ventricular paced QT interval was measured during incremental stimulation from the apical region (RVAPEX) and the outflow tract (RVOT) of the right ventricle, and the frequency dependence was analyzed using a linear regression model. At an almokalant dose of Cpl≥50, there was a significant prolongation of the MAPD of 10-15%. The prolongation was of equal magnitude at all paced cycle lengths (CL). The MAPD of ventricular extrasystoles increased in parallel over the range of coupling intervals studied and was significantly prolonged at Cpl 100 and 150. The ratio between the MAPD of the extrasystoles and preceding beats was unaltered after almokalant infusion. The ventricular paced QT intervals increased during almokalant infusion in a similar manner as that of the MAPD. During RVAPEX stimulation, the prolongation was more pronounced at low heart rates, an effect that was not seen during RVOT stimulation. Almokalant significantly prolonged the MAPD at dose levels Cpl≥50. There was no evidence of a frequency dependence of this effect. The ventricular paced QT intervals were prolonged in a similar manner as that of the MAPD, and this effect exhibited a small reverse frequency dependence during RVAPEX stimulation. Kluwer Academic Publishers, 1996 almokalant nationallicence class III antiarrhythmic drugs nationallicence monophasic action potentials nationallicence frequency dependence nationallicence ventricular paced QT intervals nationallicence Darpö Börje Department of Cardiology, Sahlgrenska Hospital, Göteborg, Sweden aut Almgren Olle Astra Hässle AB, Mölndal, Sweden aut Bergstrand Robert Astra Hässle AB, Mölndal, Sweden aut Franzén Stefan Astra Hässle AB, Mölndal, Sweden aut Edvardsson Nils Department of Cardiology, Sahlgrenska Hospital, Göteborg, Sweden aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/5(1996-11-01), 539-547 0920-3206 10:5<539 1996 10 10557 https://doi.org/10.1007/BF00050994 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00050994 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Darpö Börje Department of Cardiology, Sahlgrenska Hospital, Göteborg, Sweden aut NATIONALLICENCE 700 1- Almgren Olle Astra Hässle AB, Mölndal, Sweden aut NATIONALLICENCE 700 1- Bergstrand Robert Astra Hässle AB, Mölndal, Sweden aut NATIONALLICENCE 700 1- Franzén Stefan Astra Hässle AB, Mölndal, Sweden aut NATIONALLICENCE 700 1- Edvardsson Nils Department of Cardiology, Sahlgrenska Hospital, Göteborg, Sweden aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/5(1996-11-01), 539-547 0920-3206 10:5<539 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer