Document Detail

Azimilide decreases defibrillation voltage requirements and increases spatial organization during ventricular fibrillation.
MedLine Citation:
PMID:  10354978     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Drugs with class III antiarrhythmic properties generally decrease defibrillation threshold (DFT). However, the concentration effect relation for this effect and drug effects on ventricular fibrillation (VF) itself are not well understood. The objectives of this study were to determine the effect of azimilide (NE-10064), a new class III agent, on DFT, and on spatial organization during VF. METHODS: Defibrillation patch electrodes were sutured to the right and left ventricular epicardium in 12 open-chest anesthetized dogs. The delayed up-down algorithm was used to measure DFT and to estimate the shock strength (voltage) with a 50% probability of successful defibrillation (V50). The magnitude squared coherence (MSC), which measures the spatial relation in the frequency domain, was measured during VF between two unipolar epicardial electrodes 3 mm apart. The V50, MSC, electrophysiologic parameters, and plasma concentrations were determined before and after four cumulative i.v. doses of azimilide (2, 7, 17, and 30 mg/kg). RESULTS: Azimilide elicited a dose dependent reduction of V50 and increase in MSC. Compared with baseline, azimilide lowered mean V50 by 2 +/- 9%, 10 +/- 18%, 11 +/- 14% and 19 +/- 5%, and increased MSC by 17 +/- 20%, 32 +/- 31%, 20 +/- 44% and 27 +/- 20% (p < 0.05 for dose effect) at 2, 7, 17 and 30 mg/kg, respectively. Mean increases in monophasic action potential duration at 90% repolarization (3-11%), ventricular effective refractory period (6-13%) at 400 msec paced cycle length, and VF cycle length (5-37%) (p < 0.01 for dose effect) were observed with the 4 increasing doses of azimilide, respectively. CONCLUSION: Azimilide significantly decreases DFT and increases coherence in VF in a dose dependent manner.
X Q Qi; D Newman; P Dorian
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing     Volume:  3     ISSN:  1383-875X     ISO Abbreviation:  J Interv Card Electrophysiol     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-07-22     Completed Date:  1999-07-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9708966     Medline TA:  J Interv Card Electrophysiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  61-7     Citation Subset:  IM    
Department of Medicine, St. Michael's Hospital and University of Toronto.
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MeSH Terms
Anti-Arrhythmia Agents / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Electric Countershock*
Electrodes, Implanted
Electrophysiology / methods
Heart Rate
Imidazoles / pharmacology*
Injections, Intravenous
Piperazines / pharmacology*
Treatment Outcome
Ventricular Fibrillation / blood,  physiopathology,  therapy*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Imidazoles; 0/Imidazolidines; 0/Piperazines; 149888-94-8/azimilide

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