Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New Protocol for Safety Evaluation In Vivo

Autor: Yuji Nakamura, Suchitra Matsukura, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Xin Cao, Atsushi Sugiyama
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Time Factors
Refractory Period
Electrophysiological
Benign early repolarization
Action Potentials
Amiodarone
Blood Pressure
030204 cardiovascular system & hematology
Toxicology
Risk Assessment
QT interval
Electrocardiography
03 medical and health sciences
Dogs
0302 clinical medicine
Heart Rate
Torsades de Pointes
Internal medicine
Atrial Fibrillation
medicine
Animals
Repolarization
Molecular Biology
Dose-Response Relationship
Drug
Atrium (architecture)
business.industry
Cardiac Pacing
Artificial
Effective refractory period
Amiodarone Hydrochloride
Atrial fibrillation
medicine.disease
Disease Models
Animal
030104 developmental biology
Anesthesia
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Anti-Arrhythmia Agents
medicine.drug
Zdroj: Cardiovascular Toxicology. 17:157-162
ISSN: 1559-0259
1530-7905
DOI: 10.1007/s12012-016-9369-8
Popis: Anti-atrial fibrillatory and proarrhythmic potentials of amiodarone were simultaneously analyzed by using the halothane-anesthetized beagle dogs (n = 4) in order to begin to prepare standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of 0.3 mg/kg of amiodarone hydrochloride decreased the heart rate and mean blood pressure. Additional administration of 3 mg/kg of amiodarone hydrochloride prolonged the QT interval besides the effects observed by the low dose, whereas it showed 1.6 times larger prolongation in the effective refractory period of the atrium than that of the ventricle, which may explain its clinical efficacy against atrial arrhythmias. However, no significant change was detected by either dose in the early repolarization assessed by corrected J–T peak or the late repolarization done by T peak–T end in the electrocardiogram, although the former tended to be shortened and the reverse was true for the latter. Lack of prolongation in the early repolarization will make it feasible to better understand why amiodarone lacks proarrhythmic potential in spite of the QT-interval prolongation. Thus, these results of amiodarone obtained by current protocol may become a guidance on assessing efficacy and adverse effects of new anti-atrial fibrillatory drugs in vivo.
Databáze: OpenAIRE
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