Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest.
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.
Yoshioka
Koichiro
K
Department of Cardiology, Tokai University School of Medicine, Japan. ko1@is.icc.u-tokai.ac.jp
Amino
Mari
M
Usui
Kazutane
K
Sugimoto
Atsuhiko
A
Matsuzaki
Atsushi
A
Kohzuma
Kumiko
K
Kanda
Shigetaka
S
Deguchi
Yoshiaki
Y
Ikari
Yuji
Y
Kodama
Itsuo
I
Tanabe
Teruhisa
T
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
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant