RT Journal Article SR Electronic T1 Selective inhibition by a class III antiarrhythmic agent, E-4031, of the negative chronotropic response to parasympathetic stimulation in anesthetized dogs. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 467 OP 472 VO 276 IS 2 A1 H Imamura A1 Y Furukawa A1 H Nakano A1 M Kasama A1 Y Hoyano A1 S Chiba YR 1996 UL http://jpet.aspetjournals.org/content/276/2/467.abstract AB To investigate the influence of a class III antiarrhythmic agent, E-4031, on the vagus control of the heart, we studied the effects of E-4031 on the chronotropic, dromotropic and inotropic responses to parasympathetic stimulation in the autonomically decentralized hearts of the open-chest, anesthetized dogs. E-4031 (0.01-3 mumol/kg i.v.) decreased heart rate dose-dependently without affecting atrioventricular (AV) conduction time, first derivative of "a" wave component of the right atrial pressure (RA dP/dt), maximum rate of the right ventricular pressure development (RV +dP/dt) and arterial blood pressure. When cervical vagus stimulation decreased the heart rate, RA dP/dt and RV +dP/dt and prolonged the AV conduction time, E-4031 antagonized the negative chronotropic response in a dose-dependent manner but affected neither dromotropic nor atrial inotropic responses. E-4031 at a high dose of 3 mumol/kg i.v. attenuated the ventricular inotropic response. ID50 for the chronotropism was 0.20 +/- 0.05 mumol/kg. Stimulation of the selective intracardiac parasympathetic nerves to the sinoatrial nodal area decreased the heart rate and RA dP/dt without a dromotropic response. E-4031 antagonized the negative chronotropic response to the stimulation but not the inotropic response. Stimulation of the selective intracardiac parasympathetic nerves to the AV nodal area prolonged the AV conduction time without a chronotropic response. E-4031 at a high dose of 3 mumol/kg i.v. attenuated the negative dromotropic response to the stimulation by 35 +/- 10%. These results suggest that E-4031 preferentially blocks the negative chronotropic response to vagus stimulation without significantly affecting other cardiac responses at a site distal to the muscarinic receptor in the heart in situ.