Atrioventricular junctional rhythm induced by sympathetic stimulation in E-4031-treated dog hearts
Imamura, H.; Furukawa, Y.; Yamazaki, K.; Nakano, H.; Kasama, M.; Hoyano, Y.; Chiba, S.
Journal of Cardiovascular Pharmacology 28(4): 507-512
1996
ISSN/ISBN: 0160-2446 PMID: 8891874 Document Number: 462370
To investigate the role of delayed rectifier potassium current (I-K) on the sympathetic control of the heart, we studied the effects of E-4031, a blocker of the rapidly activating type of I-K (I-Kr), 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 mu-mol/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 I-Kr inhibition may induce the AV junctional rhythm due to the combination of the different participation of I-Kr, the different resting potentials, and the different sensitivity to sympathetic activation among cardiac pacemaker cells.