Abstract 2861: Amiodarone, in Contrast to Sotalol, Equally Decreases Epicardial and Endocardial Atrial Fibrillation Inducibility, Despite a Steep Transmural Concentration Gradient
Background: Amiodarone causes less ventricular transmural dispersion of repolarization (TDR) and proarrhythmia than sotalol. Effects of both drugs on atrial TDR, however, have not yet been well defined. We applied intrapericardial (IPC) drug delivery to produce in vivo transmural concentration gradients. We assessed the hypotheses that IPC amiodarone causes less atrial TDR than IPC sotalol and that IPC amiodarone is more effective than IPC sotalol in lowering atrial fibrillation (AF) inducibility.
Methods: Goats (n = 25) were randomised into 5 groups receiving either IPC dextrose, amiodarone (IV or IPC) or d,l-sotalol (IV or IPC). Drugs were infused for 3 hours at a constant rate of 2 mg/kg per hour. Quadripolar catheters were placed on the epi- and endocardial surfaces of the right atrium. Atrial effective refractory period (AERP) and AF inducibility were measured by single premature stimuli at 4 times the diastolic threshold. Atria were freeze-microtomed parallel to the epicardial surface and analysed by HPLC.
Results: IPC drug delivery produced high epicardial concentrations (fig.1a⇓) with significantly decreased epicardial AF inducibility. A similar decrease in endocardial AF inducibility was only observed in the IPC amiodarone group (fig.1b⇓). TDR (defined as endo-minus epicardial AERP) became negative after IPC sotalol (from 13.0 ± 3.2 to -30.7 ± 7.3 ms, p < 0.05). In the other groups TDR did not change significantly and remained positive.
Conclusions: IPC delivery boosts epicardial drug concentration and efficacy. For amiodarone, this also increases endocardial efficacy. IPC sotalol, however, inverts TDR, which may explain its inferior endocardial efficacy.