title: Termination of Atrial Flutter and Fibrillation by K201's Metabolite M-II: Studies in the Canine Sterile Pericarditis Model.
abstract: BACKGROUND
  K201, a 1,4-benzodiazepine derivative, acts on multiple cardiac ion channels and the ryanodine receptor. We tested whether administration of M-II, the main metabolite of K201, would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model.
  
  
  METHODS
  In 6 dogs, electrophysiologic studies were performed at baseline and after drug administration, measuring atrial effective refractory period (AERP), and conduction time from 3 sites during pacing at cycle lengths (400, 300, and 200 milliseconds) on postoperative days 1-4. In 12 induced episodes of sustained AF/AFL (2/10, respectively), M-II was administered intravenously to test efficacy. Five of the AFL episodes were studied in the open chest state during simultaneous multisite atrial mapping.
  
  
  RESULTS
  M-II terminated 2/2 AF and 8/10 AFL episodes, prolonged AERP (P < 0.05), significantly increased atrial pacing capture thresholds but did not significantly change atrial conduction time. AFL CL prolongation was largely explained by prolonged conduction in an area of slow conduction in the reentrant circuit. AFL terminated with block in the area of slow conduction.
  
  
  CONCLUSIONS
  M-II was very effective in terminating AFL/AF in the canine sterile pericarditis model. AFL terminated due to block in the area of slow conduction of the reentrant circuit.
authors: *Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH; and †Sequel Pharmaceuticals, Inc., San Diego, CA. T. Fields and H. C. Dittrich are now with Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA.
authors: Shervin A
authors: SA
authors: Sadrpour
authors: Maya
authors: M
authors: Serhal
authors: Celeen M
authors: CM
authors: Khrestian
authors: Seungyup
authors: S
authors: Lee
authors: Tara
authors: T
authors: Fields
authors: Howard C
authors: HC
authors: Dittrich
authors: Albert L
authors: AL
authors: Waldo
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001282:Atrial Flutter / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001711:Biotransformation; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D010493:Pericarditis / Q000150:complications*; D013841:Thiazepines / Q000378:metabolism / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; C510846:M-II compound; D013841:Thiazepines; D045162:Thiazolidinediones; C109183:K201 compound