[Electrophysiological effects of antiarrhythmic drug UK-68798 on different AV nodal cells in rabbit heart].
By means of microelectrode techniques the electrophysiological effects of a new class III antiarrhythmic agent, UK-68798 (Dofetilide), were investigated on atrionodal (AN), nodal (N), nodal-His (NH) and His (H) cells in the AVN area of rabbit heart. UK-68798 (5 x 10(-9) to 5 x 10(-6) mol/L) had no effect on APA and RP of the 4 kinds of cells but caused a dose-dependent decrease in AVN spontaneous rhythm without changing the A-H conduction time. APD50 and APD90 were prolonged markedly by the drug in a dose-dependent manner. Among the 4 kinds of cells, N cell had the highest percentage increment in APD, indicating a prominent sensitivity to the drug. For example, at 5 x 10(-6) mol/L, the prolongation percentages of APD90 are: 95 +/- 26% (N), 75 +/- 22% (AN), 63 +/- 26% (H), 46 +/- 26% (NH). The effective refractory periods (ERP) of the 4 kinds of cells were lengthened also in a dose-dependent manner, while the ERP increment percentages (delta ERP%) of the 4 kinds of cells did not show significant difference. However, ERP corresponding repolarization membrane potentials (ERP-RMP) of the 4 kinds of cells were not affected by the drug. The above results suggested that though ERP increased in parallel with APD prolongation, the homogeneous delta ERP% and unchanged ERP-RMP values of the 4 kinds of cells would prevent the AVN area from becoming a source of reentry arrhythmias under the action of UK-68798.
Department of Biology, Beijing University.
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TL
Gao
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Beyer
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Brachmann
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000166:cytology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008839:Microelectrodes; D010627:Phenethylamines / Q000494:pharmacology*; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide