title: Preserved effects of potassium channel blockers in the pacing-induced remodeled canine atrium: a comparison between E4031 and azimilide.
abstract: This study was designed to evaluate the electrophysiologic effects of E4031 (a pure IKr blocker) and azimilide (AZ: a combined Ikr + IKs blocker) at various stages of atrial electrical remodeling. Twelve dogs underwent continuous rapid atrial pacing (400/min) for 14 days. The electrophysiologic study was performed on the day before as well as after 2, 7, and 14 days of rapid atrial pacing both before and after the administration of either E4031 (n = 6) or AZ (n = 6). In response to rapid atrial pacing, the atrial effective refractory period (ERP), conduction velocity, and wavelength decreased significantly at pacing cycle lengths (PCLs) of 200 and 400 ms (P < 0.05). E4031 prolonged ERP in a reverse use-dependent manner throughout the study period. AZ also prolonged ERP during the 14 days of rapid pacing. ERP prolongation at a PCL of 200 ms was significantly greater with AZ than with E4031 (P < 0.05). The effects of blocking IKr by E4031 and IKr + IKs by AZ were well preserved at various stages of atrial electrical remodeling. However, the effect of prolonging ERP at a shorter PCL was more prominent by AZ than by E4031. Thus, IKs blockade may add a favorable anti-fibrillatory effect to IKr blockade even in the remodeled atrium.
authors.affiliation: Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiroshita-Takeshita
authors.forename: Hideo
authors.initials: H
authors.lastname: Mitamura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sato
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinagawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurita
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kanki
authors.forename: Seiji
authors.initials: S
authors.lastname: Takatsuki
authors.forename: Motoki
authors.initials: M
authors.lastname: Hara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004567:Electrodes, Implanted; D005260:Female; D006827:Hydantoins; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
chemical_list: D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; D010880:Piperidines; D026902:Potassium Channel Blockers; D011725:Pyridines; C063968:E 4031; C086123:azimilide