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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

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 (1 mg/ 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 28 days 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 21 days after application. In this period, AERP and conduction time were prolonged, while RAR inducibility was reduced (P b0.05) 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 (b10 ng/ mL) during the 28-day follow-up. Conclusions: Epicardial application of an amiodarone-releasing hydrogel reduces atrial vulnerability to tachyarrhythmias up to 3 weeks, while extracardiac drug levels remain low. Therefore, amiodaronereleasing hydrogel could be applied during cardiac surgery to prevent postoperative AF at minimal risk for extracardiac adverse side effects. c 2010
Original languageEnglish
Pages (from-to)341-346
JournalInternational Journal of Cardiology
Volume149
Issue number3
DOIs
Publication statusPublished - 16 Jun 2011

Keywords

  • Amiodarone
  • Arrhythmia
  • Atrium
  • Hydrogel
  • Local drug delivery

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