Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias.
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.
Bolderman
Robert W
RW
Cardiovascular Research Institute Maastricht, Department of Cardiothoracic Surgery, Maastricht, The Netherlands. r.bolderman@ctc.unimaas.nl
Hermans
J J Rob
JJ
Rademakers
Leonard M
LM
de Jong
Monique M J
MM
Bruin
Peter
P
Dias
Aylvin A
AA
van der Veen
Frederik H
FH
Maessen
Jos G
JG
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*
D000889:Anti-Arrhythmia Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C036116:desethylamiodarone; D000638:Amiodarone