caa a22 4500 477072623 CHVBK 20180405111430.0 cr unu---uuuuu 170330e19961101xx s 000 0 eng 10.1007/BF00050993 doi (NATIONALLICENCE)springer-10.1007/BF00050993 Effects of AWD 23-111, a new antiarrhythmic substance, on cardiac conduction and refractoriness [Elektronische Daten] [Ulrike Stark, Gerhard Stark, Ingrid Schwarzl, Hildegard Poppe, Degenhard Marx, Martin Decrinis, Helmut Tritthart] Summary: In isolated spontaneously beating guinea pig hearts, the effects of AWD 23-111 (N-(dicyclohexylcarbamoylmethyl)-N-(3-diethylamino-propyl)-4-nitrobenzamid-hydrochloride), a new synthetic class III antiarrhythmic agent with sodium antagonistic properties, were investigated on cardiac electrophysiological parameters, that is, conduction and refractoriness. Concentration-dependent prolongation of the atrioventricular, intraventricular, and His bundle conduction times and of sinus node cycle length were present. At 0.3 μM the repolarization period was prolonged significantly. No reverse use-dependent effect on the repolarization period was observed. During rapid pacing (pacing cycle length = 120 ms for the ventricle and 180 ms for the atrium) the rate-dependent intraventricular (QRS) or atrioventricular conduction time (AVCT) prolongation follows an exponential function of the beat number and is characterized by a drug-specific time constant. The time constant for the intraventricular conduction time prolongation in the presence of 0.1 μM AWD 23-111 was very long at 150±29 beats (mean±SEM; n=6), indicating a slow binding kinetic to the sodium channel. At 0.1 μM AWD 23-111, a significant increase in the ventricular effective refractory period was reached when the interstimulus interval (S1-S1) was 120 ms and the number of conditioning stimuli (S1) was higher than the time constant. The time constant for the rate-dependent AVCT prolongation in the presence of 0.3 μM AWD 23-111 was 34±6 beats (n=6). The effective refractory period of the atrioventricular conduction significantly increased with the number of conditioning stimuli (S1), until the number was comparable with the time constant. In conclusion, AWD 23-111 exerts a wide variety of actions on the cardiac conduction system. Its combined effects on the potassium and sodium channels seem to be responsible for the marked rate-dependent effect on ventricular refractoriness and for the lack of a reverse use-dependency on JT prolongation. Kluwer Academic Publishers, 1996 AWD 23-111 nationallicence conduction intervals nationallicence sinus rate nationallicence rate dependency nationallicence refractoriness nationallicence time constant nationallicence repolarization period nationallicence Langendorff nationallicence guinea pig nationallicence Stark Ulrike Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut Stark Gerhard Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut Schwarzl Ingrid Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut Poppe Hildegard Arzheimittelwerk Dresden GmbH, Dresden, Germany aut Marx Degenhard Arzheimittelwerk Dresden GmbH, Dresden, Germany aut Decrinis Martin Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut Tritthart Helmut Department of Medical Physics and Biophysics, Karl-Franzens-University, Graz, Austria aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/5(1996-11-01), 531-538 0920-3206 10:5<531 1996 10 10557 https://doi.org/10.1007/BF00050993 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00050993 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stark Ulrike Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut NATIONALLICENCE 700 1- Stark Gerhard Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut NATIONALLICENCE 700 1- Schwarzl Ingrid Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut NATIONALLICENCE 700 1- Poppe Hildegard Arzheimittelwerk Dresden GmbH, Dresden, Germany aut NATIONALLICENCE 700 1- Marx Degenhard Arzheimittelwerk Dresden GmbH, Dresden, Germany aut NATIONALLICENCE 700 1- Decrinis Martin Department of Internal Medicine, Karl-Franzens-University, Graz, Austria aut NATIONALLICENCE 700 1- Tritthart Helmut Department of Medical Physics and Biophysics, Karl-Franzens-University, Graz, Austria aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/5(1996-11-01), 531-538 0920-3206 10:5<531 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer