Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats

Nikolett Morvay, I. Baczkó, Anita Sztojkov-Ivanov, G. Falkay, J. Papp, A. Varró, I. Leprán

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)773-777
Number of pages5
JournalCanadian Journal of Physiology and Pharmacology
Volume93
Issue number9
DOIs
Publication statusPublished - Apr 15 2015

Fingerprint

Amiodarone
Coronary Occlusion
Cardiac Arrhythmias
Coronary Vessels
Myocardial Infarction
Silk
Ligation
desethylamiodarone

Keywords

  • Amiodarone
  • Arrhythmias
  • Desethylamiodarone
  • Myocardial infarction
  • Rats
  • Survival

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

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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.",
keywords = "Amiodarone, Arrhythmias, Desethylamiodarone, Myocardial infarction, Rats, Survival",
author = "Nikolett Morvay and I. Baczk{\'o} and Anita Sztojkov-Ivanov and G. Falkay and J. Papp and A. Varr{\'o} and I. Lepr{\'a}n",
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T1 - Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats

AU - Morvay, Nikolett

AU - Baczkó, I.

AU - Sztojkov-Ivanov, Anita

AU - Falkay, G.

AU - Papp, J.

AU - Varró, A.

AU - Leprán, I.

PY - 2015/4/15

Y1 - 2015/4/15

N2 - 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.

AB - 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.

KW - Amiodarone

KW - Arrhythmias

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KW - Myocardial infarction

KW - Rats

KW - Survival

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