Atrioventricular junctional rhythm induced by sympathetic stimulation in E-4031-treated dog hearts

To investigate the role of delayed rectifier potassium current (IK) on the sympathetic control of the heart, we studied the effects of E-4031, a blocker of the rapidly activating type of IK (IKr), on the chronotropic, dromotropic, and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized hearts of open-chest anesthetized dogs, E-4031 (0.01-3 mumol/kg intravenously, i.v.) decreased the heart rate (HR) dose dependently without affecting other cardiac functions. After E-4031 treatment, cardiac sympathetic nerve stimulation changed the sinus rhythm to the atrioventricular (AV) junctional rhythm in 6 of 11 anesthetized dogs (55%). In three of six junctional rhythm hearts, sinus rhythm supervened during sympathetic stimulation for 2 min. The number of pacemaker shifts to junctional rhythm increased as the dose of E-4031 was increased. However, E-4031 attenuated neither the positive chronotropic, dromotropic, nor right atrial and ventricular inotropic responses to sympathetic nerve stimulation. These results suggest that IKr inhibition may induce the AV junctional rhythm due to the combination of the different participation of IKr, the different resting potentials, and the different sensitivity to sympathetic activation among cardiac pacemaker cells.