title: Influences of rapid pacing-induced electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits.
abstract: Electrical remodeling plays a pivotal role in maintaining the reentry during atrial fibrillation. In this study, we assessed influence of electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits. We used an atrial electrical remodeling model of the rabbit, subjected to rapid atrial pacing (RAP; 600 beats/min) for 2-4 weeks, leading to shortening of atrial effective refractory period (AERP). Intravenous administration of dl-sotalol (6 mg/kg), bepridil (1 mg/kg), amiodarone (10 mg/kg) or vernakalant (3 mg/kg) significantly prolonged the AERP both in the control and RAP rabbits. The extents in the RAP rabbits were similar to those in the control animals. On the other hand, prolonging effects of intravenously administered ranolazine (10 mg/kg) or tertiapin-Q (0.03 mg/kg) on the AERP in the RAP rabbits were more potent than those in the control animals. These results suggest that rapid pacing-induced electrical remodeling effectively modified the prolonging effects of ranolazine and tertiapin-Q on the AERP in contrast to those of clinically available antiarrhythmic drugs, dl-sotalol, bepridil amiodarone and vernakalant.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan; Department of R&D, Fukushima Research Laboratories, TOA EIYO Ltd., Iizaka, Fukushima 960-0211, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of R&D, Fukushima Research Laboratories, TOA EIYO Ltd., Iizaka, Fukushima 960-0211, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. Electronic address: akirat@phar.toho-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*; D064752:Atrial Remodeling / Q000187:drug effects* / Q000502:physiology*; D015764:Bepridil / Q000008:administration & dosage / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008297:Male; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013015:Sotalol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D015764:Bepridil; C524581:vernakalant; D013015:Sotalol; D000638:Amiodarone
keywords: Antiarrhythmic drugs; Atrial fibrillation; Effective refractory period; Electrical remodeling