title: Atrial-selective inhibition of sodium-channel current by Wenxin Keli is effective in suppressing atrial fibrillation.
abstract: BACKGROUND
  Wenxin Keli is a Chinese herb extract reported to be of benefit in the treatment of cardiac arrhythmias, cardiac inflammation, and heart failure.
  
  
  RESULTS
  We evaluated the electrophysiologic effects of Wenxin Keli in isolated canine arterially perfused right atrial preparations with a rim of right ventricular tissue (n = 11). Transmembrane action potentials and a pseudoelectrocardiogram were simultaneously recorded. Acetylcholine (1 μM) was used to induce atrial fibrillation (AF) and to test the anti-AF potential of Wenxin Keli (5 g/L). Wenxin Keli produced preferential abbreviation of action potential duration measured at 90% repolarization (APD(90)) in atria, but caused atrial-selective prolongation of the effective refractory period, due to the development of postrepolarization refractoriness. The maximum rate of rise of the action potential upstroke was preferentially reduced in atria. The diastolic threshold of excitation increased in both atria and ventricles, but much more in atria. The duration of the "P wave" (index of atrial conduction time) was prolonged to a much greater extent than the duration of the "QRS complex" (index of ventricular conduction time). Wenxin Keli significantly reduced I(Na) and shifted steady-state inactivation to more negative potentials in HEK293 cells stably expressing SCN5A. Wenxin Keli prevented the induction of persistent AF in 100% atria (6/6) and, in another experimental series, was found to terminate persistent acetylcholine-mediated AF in 100% of atria (3/3).
  
  
  CONCLUSIONS
  Wenxin Keli produces atrial-selective depression of I(Na)-dependent parameters in canine isolated coronary-perfused preparations via a unique mechanism and is effective in suppressing AF and preventing its induction, with minimal effects on the ventricular electrophysiology.
authors: Masonic Medical Research Laboratory, Utica, New York 13501, USA.
authors: Alexander
authors: A
authors: Burashnikov
authors: Alyssa
authors: A
authors: Petroski
authors: Dan
authors: D
authors: Hu
authors: Hector
authors: H
authors: Barajas-Martinez
authors: Charles
authors: C
authors: Antzelevitch
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D055724:Electrophysiological Phenomena / Q000187:drug effects; D057809:HEK293 Cells; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004365:Drugs, Chinese Herbal; D026941:Sodium Channel Blockers; C532373:wenxin keli