title: Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias.
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.
authors.affiliation: Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands. r.bolderman@ctc.unimaas.nl
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bolderman
authors.forename: J J Rob
authors.initials: JJ
authors.lastname: Hermans
authors.forename: Leonard M
authors.initials: LM
authors.lastname: Rademakers
authors.forename: Monique M J
authors.initials: MM
authors.lastname: de Jong
authors.forename: Peter
authors.initials: P
authors.lastname: Bruin
authors.forename: Aylvin A
authors.initials: AA
authors.lastname: Dias
authors.forename: Frederik H
authors.initials: FH
authors.lastname: van der Veen
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
mesh_terms: D000279:Administration, Cutaneous; D000638:Amiodarone / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004567:Electrodes, Implanted; D006041:Goats; D006325:Heart Atria / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D010496:Pericardium / Q000187:drug effects*; D011092:Polyethylene Glycols; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013612:Tachycardia, Ectopic Atrial / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C036116:desethylamiodarone; D000638:Amiodarone