Europace Advance Access published online on September 21, 2007
Europace, doi:10.1093/europace/eum196
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Comparative effects of acute vs. chronic oral amiodarone treatment during acute myocardial infarction in rats
1 Department of Cardiology, University of Ioannina, 1 Stavrou Niarxou Avenue, 45110 Ioannina, Greece; 2 Department of Child Health, University of Ioannina, 1 Stavrou Niarxou Avenue, 45110 Ioannina, Greece; 3 Department of Pharmacology, University of Athens, Goudi, Athens, Greece; 4 Department of Nuclear Medicine, University of Ioannina, 1 Stavrou Niarxou Avenue, 45110 Ioannina, Greece
Aims: This study investigated whether chronic and acute amiodarone treatment has differential effects on ventricular arrhythmogenesis during acute myocardial infarction in rats.
Methods and results: Forty-six rats were randomly allocated into vehicle, chronic oral amiodarone (30 mg/kg daily for 2 weeks), or acute amiodarone (a single dose, 100 mg/kg). Five additional rats were sham-operated. Myocardial infarction was generated by left coronary artery ligation 2 weeks after chronic treatment. Amiodarone was administered acutely 5 min post-ligation. The electrocardiogram was recorded for 24 h, using an implanted telemetry transmitter. Episodes of ventricular tachyarrhythmias and mortality rates were analysed. Serum catecholamines and infarct size were measured 24 h post-ligation. No differences were found in infarct size. Compared with controls (22.7 ± 10.9), there was a similar reduction in the number of tachyarrhythmia episodes after either chronic (2.6 ± 1.6, P = 0.0011) or acute (3.6 ± 1.7, P = 0.031) amiodarone administration. Norepinephrine levels were lower only after chronic treatment. Mortality in both amiodarone treatment arms was exclusively due to bradyarrhythmia secondary to cardiac failure, whereas mortality in controls was mainly attributed to tachyarrhythmic death.
Conclusions: A rapid antiarrhythmic effect was observed after acute amiodarone administration in the rat. Norepinephrine levels decreased after chronic treatment and may be associated with bradyarrhythmic mortality.
Key Words: Myocardial infarction, Ventricular tachyarrhythmias, Amiodarone, Loading dosage, Catecholamines, Mortality
* Corresponding author. Tel: +30 2651097227; fax: +30 2651097053. E-mail address: thkolet{at}cc.uoi.gr
Manuscript submitted 6 July 2007. Accepted after revision 13 August 2007.