Effects of amiodarone and dronedarone on heart rate variability, cardiac contractility, and thyroid hormone levels in rabbits

Abstract

Amiodarone (AM) and dronedarone (DR) are class III antiarrhythmic agents that have similar chemical structures, except AM contains iodine molecules. Due to the limited data available in rabbits, the effects of both drugs on heart rate variability (HRV), contractility and thyroid hormone levels were studied. Sixteen male New Zealand white rabbits were used and divided into 2 groups received AM or DR. The rabbits were gavaged either AM or DR at dosages of 50 (AM50, DR50) and 100 mg/kg/day (AM100, DR100) continuously for a period of 7 days each. On the last day of each period, electrocardiograms were recorded from the conscious rabbits, while standard echocardiograms (Echo), speckle tracking echocardiograms (STE) and blood samples were collected from the anesthetized rabbits afterward. The HRV results showed that AM100 and DR100 decreased heart rate, total power, low frequency component, and low to high frequency ratio significantly compared to the baselines. All echocardiographic parameters of both agents in every period were no significant difference from their baselines, except global circumferential plane strain rate at basal segmental level of AM50 that was decreased. Thyroxine levels were significantly increased in AM treatments but decreased in DR treatments of treatment period 1 and 2 compared to their baseline. In conclusion, both AM and DR reduce HRV which may be due to sympathetic suppression. STE may provide more information but not give higher sensitivity than Echo in our study, despite the fact that AM may have more negative inotropic effect than DR in this model. Nevertheless, both drugs produced thyroid dysfunction in the different way, thyrotoxicosis in AM but hypothyroidism in DR.