title: Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest.
abstract: BACKGROUND
  Because nifekalant hydrochloride (NIF) displayed a superior defibrillating effect on ventricular tachycardia/fibrillation (VT/VF) in cardiopulmonary arrest (CPA) patients, despite some QT prolongation, its effect on transmural dispersion of repolarization (TDR) in the left ventricle (LV) in an animal model of CPA was investigated.
  
  
  RESULTS
  Eight beagle dogs were created with a myocardial infarction under anesthesia, and then VT/VF induction by continuous stimulation and cardiopulmonary resuscitation (CPR) were repeated. NIF (0.3 mg/kg) was administered under acidotic conditions (pH 7.26). The QTc interval measured by Y-lead ECG showed no significant prolongation before and after NIF. The activation recovery interval (ARI) measured by 64-lead LV surface mapping showed minimum ARI prolongation (40%) by NIF without maximum ARI prolongation, and as a result the ARI dispersion decreased by 67%. The repolarization time (RPT) with the plunge electrode showed 13-19% prolongation in the subendocardium and subepicardium with CPR, but NIF prolonged the RPT in the middle layer alone (17%), and as a result Plunge-TDR decreased by 82% (n=8, p<0.05).
  
  
  CONCLUSIONS
  Administration of NIF during CPR decreased the TDR by RPT prolongation selectively in the middle layer. Because the subendocardial and subepicardial RPTs after CPR were already prolonged before NIF administration, it may have been the reason why the QT-prolonging effect of NIF was not reflected in the body surface ECG.
authors.affiliation: Department of Cardiology, Tokai University School of Medicine, Japan. ko1@is.icc.u-tokai.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Mari
authors.initials: M
authors.lastname: Amino
authors.forename: Kazutane
authors.initials: K
authors.lastname: Usui
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsuzaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kohzuma
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Kanda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Deguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikari
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D006323:Heart Arrest / Q000628:therapy*; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D011744:Pyrimidinones / Q000008:administration & dosage*; D017180:Tachycardia, Ventricular / Q000628:therapy; D014693:Ventricular Fibrillation / Q000628:therapy
chemical_list: D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant