Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias

Bolderman, Robert W.; Hermans, J.J. Rob; Rademakers, Leonard M.; de Jong, Monique M.J.; Bruin, Peter; Dias, Aylvin A.; van der Veen, Frederik H.; Maessen, Jos G.

doi:10.1016/j.ijcard.2010.02.014

« Previous Next »International Journal of Cardiology
Volume 149, Issue 3 , Pages 341-346, 16 June 2011

Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias

Robert W. Bolderman
- Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands
- Corresponding author. Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Universiteitssingel 50, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Tel.: +31 43 3881066; fax: +31 43 3877075.
J.J. Rob Hermans
- Cardiovascular Research Institute Maastricht, Department of Pharmacology, Maastricht, The Netherlands
Leonard M. Rademakers
- Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands
Monique M.J. de Jong
- Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands
Peter Bruin
- DSM Biomedical, Geleen, The Netherlands
Aylvin A. Dias
- DSM Biomedical, Geleen, The Netherlands
Frederik H. van der Veen
- Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands
Jos G. Maessen
- Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands

Received 1 November 2009; received in revised form 18 December 2009; accepted 6 February 2010. published online 08 March 2010.

Abstract

Background

Amiodarone is currently the most effective antiarrhythmic drug for sinus rhythm maintenance. However, due to serious extracardiac adverse effects, prophylactic amiodarone therapy is only appropriate for patients at high risk for postoperative atrial fibrillation (AF). We hypothesized that epicardial application of an amiodarone-releasing hydrogel would produce therapeutic myocardial drug concentrations, while systemic levels would remain low.

Methods

Goats were fitted with right atrial epicardial patch electrodes. A poly(ethylene glycol)-based hydrogel with amiodarone (1mg/kg bw) (n=10) or without drug (n=6) was applied to the right atrial epicardium. Atrial effective refractory period (AERP), conduction time and atrial response to burst pacing (rapid atrial response, RAR) were assessed up to 28days in awake goats. Myocardial, plasma and extracardiac tissue amiodarone concentrations were analysed by high-performance liquid chromatography.

Results

The amiodarone-loaded hydrogel produced therapeutic drug concentrations in the right atrium up to 21days after application. In this period, AERP and conduction time were prolonged, while RAR inducibility was reduced (P<0.05) compared to animals treated with drug-free hydrogel. Mean amiodarone concentrations in the right atrium were 1 order of magnitude higher than in other heart chambers and 2 orders of magnitude higher than in extracardiac tissues. Plasma amiodarone levels remained below the detection limit (<10ng/mL) during the 28-day follow-up.

Conclusions

Epicardial application of an amiodarone-releasing hydrogel reduces atrial vulnerability to tachyarrhythmias up to 3weeks, while extracardiac drug levels remain low. Therefore, amiodarone-releasing hydrogel could be applied during cardiac surgery to prevent postoperative AF at minimal risk for extracardiac adverse side effects.

Keywords: Amiodarone, Arrhythmia, Atrium, Hydrogel, Local drug delivery