Original ArticleAZD1305 Exerts Atrial Predominant Electrophysiological Actions and Is Effective in Suppressing Atrial Fibrillation and Preventing Its Reinduction in the DogBurashnikov, Alexander PhD*; Zygmunt, Andrew C PhD*; Di Diego, Jose M MD*; Linhardt, Gunilla MSc†; Carlsson, Leif PhD†; Antzelevitch, Charles PhD*Author Information From the *Masonic Medical Research Laboratory, Utica, NY; and †Department of Bioscience, AstraZeneca R&D, Mölndal, Sweden. Received for publication February 11, 2010; accepted March 30, 2010. Supported by a grant from AstraZeneca R&D, Mölndal, Sweden, grant HL47678 from the National Heart, Lung, and Blood Institute (C. Antzelevitch) and the Free and Accepted Masons of New York State and Florida. Conflict of Interest Disclosure: Dr. L. Carlsson and G. Linhardt are employees of AstraZeneca R&D. Dr. C. Antzelevitch received a grant from AstraZeneca R&D. Reprints: Charles Antzelevitch, PhD, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501 (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: July 2010 - Volume 56 - Issue 1 - p 80-90 doi: 10.1097/FJC.0b013e3181e0bc6b Buy Metrics Abstract Recent development of drugs for the treatment of atrial fibrillation (AF) has focused on atrial selective agents. We examined the atrioventricular differences in sodium channel block of the antiarrhythmic agent AZD1305 in atria and ventricles of anesthetized dogs in vivo, canine isolated arterially perfused preparations in vitro, and isolated myocytes using whole-cell patch-clamp techniques. AZD1305 did not change heart rate or blood pressure in vivo but prolonged action potential duration and increased effective refractory period, diastolic threshold of excitation, and conduction time preferentially in atria both in vitro and in vivo. AZD1305 reduced the maximum rate of rise of the action potential upstroke (Vmax) predominantly in atria (−51% ± 10% in atria vs. −31% ± 23% in ventricles; 3 μM; cycle length = 500 milliseconds). Fast sodium current (INa) was blocked by AZD1305 to a greater degree in atrial versus ventricular myocytes (particularly tonic inhibition). In coronary-perfused right atria, AZD1305 very effectively prevented induction of persistent acetylcholine-mediated AF and, in a different set of atria, terminated persistent AF (in 5 of 5 and 7 of 8 atria, respectively). In conclusion, AZD1305 exerts atrial predominant sodium channel-blocking effects in vitro and in vivo and effectively suppresses AF. © 2010 Lippincott Williams & Wilkins, Inc.