Roles of IK,ACh for perpetuating atrial fibrillation: Effects of atrial-selective K+ channel inhibitor AVE0118 and class I drugs on the persistent atrial fibrillation canine model

  • J Pharmacol Sci. 2022 Aug;149(4):175-178. doi: 10.1016/j.jphs.2022.05.004.
Ryuichi Kambayashi  1 ,  Ai Goto  1 ,  Hiroko Izumi-Nakaseko  1 ,  Yoshinori Takei  1 ,  Akio Matsumoto  2 ,  Shinichi Kawai  3 ,  Atsushi Sugiyama  4
Affiliations
  • 1. Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
  • 2. Department of Aging Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
  • 3. Department of Inflammation & Pain Control Research, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
  • 4. Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Department of Aging Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Department of Inflammation & Pain Control Research, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Yamanashi Research Center of Clinical Pharmacology, 73-5 Hatta, Fuefuki-city, Yamanashi 406-0023, Japan. Electronic address: [email protected].
PMID: 35717070 DOI: 10.1016/j.jphs.2022.05.004
Abstract

Since information is still limited whether atrial IK,ACh may become a potential therapeutic target to terminate persistent atrial fibrillation (AF), we assessed it by using the persistent AF canine model with representative IK,ACh inhibitor AVE0118 and class I drugs. AVE0118 (6 mg/kg, n = 7), disopyramide (3 mg/kg, n = 7) and cibenzoline (3 mg/kg, n = 6) terminated the AF in 3/7, 1/7 and 2/6 Animals, respectively, whereas aprindine (3 mg/kg, n = 6) did not suppress it. These findings suggest that IK,ACh inhibition in addition to open-state INa suppression with slow dissociation kinetics can synergistically exert potent antiarrhythmic action against persistent AF.

Keywords
AVE0118; I(K,ACh); Persistent AF.
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