title: Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats.
abstract: The aim of this investigation was to compare the effectiveness of long-term pretreatment with amiodarone (AMIO) and its active metabolite desethylamiodarone (DEA) on arrhythmias induced by acute myocardial infarction in rats. Acute myocardial infarction was induced in conscious, male, Sprague-Dawley rats by pulling a previously inserted loose silk loop around the left main coronary artery. Long-term oral pretreatment with AMIO (30 or 100 mg·(kg body mass)(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days) or DEA (15 or 50 mg·kg(-1)·day(-1), loading dose 100 or 300 mg·kg(-1) for 3 days), was applied for 1 month before the coronary artery occlusion. Chronic oral treatment with DEA (50 mg·kg(-1)·day(-1)) resulted in a similar myocardial DEA concentration as chronic AMIO treatment (100 mg·kg(-1)·day(-1)) in rats (7.4 ± 0.7 μg·g(-1) and 8.9 ± 2.2 μg·g(-1)). Both pretreatments in the larger doses significantly improved the survival rate during the acute phase of experimental myocardial infarction (82% and 64% by AMIO and DEA, respectively, vs. 31% in controls). Our results demonstrate that chronic oral treatment with DEA resulted in similar cardiac tissue levels to that of chronic AMIO treatment, and offered an equivalent degree of antiarrhythmic effect against acute coronary artery ligation induced ventricular arrhythmias in conscious rats.
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, H-6701 Szeged, Dóm tér 12, Hungary.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Morvay
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, H-6701 Szeged, Dóm tér 12, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Baczkó
authors.affiliation: b Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Sztojkov-Ivanov
authors.affiliation: b Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Falkay
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, H-6701 Szeged, Dóm tér 12, Hungary.|c MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, H-6701 Szeged, Dóm tér 12, Hungary.|c MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, H-6701 Szeged, Dóm tér 12, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Leprán
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000150:complications* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003243:Consciousness; D054059:Coronary Occlusion / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; C036116:desethylamiodarone; D000638:Amiodarone
keywords: amiodarone; arrhythmias; arythmies; desethylamiodarone; déséthylamiodarone; infarctus du myocarde; myocardial infarction; rats; survie; survival