title: Electrophysiologic mechanism of typical atrial flutter termination by nifekalant: effect of a pure IKr -selective blocking agent.
abstract: BACKGROUND
  Little is known about the effect of nifekalant, a pure I(Kr) -selective blocker, on typical atrial flutter (AFL) and its termination mechanism.
  
  
  METHODS
  The effects of nifekalant on AFL were elucidated in 17 patients. During AFL, the conduction time from the lateral to septal cavotricuspid isthmus (IS) and that through the reminder of the right atrium (nIS); AFL-cycle length (CL) variability, which was quantified by the standard deviation; and the maximum difference in AFL-CL were measured before and after administration of nifekalant (0.2-0.3 mg/kg). A single extrastimulus was delivered from the lateral cavotricuspid isthmus to elucidate the resetting response curves and atrial effective refractory period (AERP) before and after administration of nifekalant.
  
  
  RESULTS
  There was no significant difference in AFL-CL, IS, and nIS before and after nifekalant; however, AERP was increased after nifekalant (155 ± 22 ms vs 184 ± 32 ms, P < 0.001). The standard deviation and the maximum difference in AFL-CL were both increased after nifekalant (1.7 ± 0.7 ms vs 3.6 ± 2.3 ms, P < 0.001 and 4.1 ± 1.9 ms vs 8.5 ± 5.2 ms, P < 0.001). The total excitable gap decreased (94 ± 17 ms vs 66 ± 21 ms, P < 0.001) with rightward shift of the resetting response curves and loss of full excitability after nifekalant. In 11 patients (65%), AFL was terminated spontaneously (n = 7) or by a single extrastimulus (n = 4), which was not observed before nifekalant. Termination was associated with orthodromic block in the cavotricuspid isthmus in all patients.
  
  
  CONCLUSIONS
  Nifekalant increases AERP and AFL-CL variability by abolishing a fully excitable gap, without prolongation of AFL-CL. These unique effects facilitate the termination of AFL.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yamabe
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Morihisa
authors.forename: Takashi
authors.initials: T
authors.lastname: Uemura
authors.forename: Junjiroh
authors.initials: J
authors.lastname: Koyama
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hoshiyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology*; D018780:Body Surface Potential Mapping / Q000187:drug effects*; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D011744:Pyrimidinones; C076259:nifekalant
keywords: SVT; electrophysiology-clinical; mapping