TY - JOUR
T1 - Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch
AU - Bolderman, Robert W.
AU - de Bruin, Jan Peter
AU - Hermans, J. J. Rob
AU - Boerakker, Mark J.
AU - Dias, Aylvin A.
AU - van der Veen, Frederik H.
AU - Maessen, Jos G.
PY - 2010/10
Y1 - 2010/10
N2 - Objective: Clinical studies have demonstrated the efficacy of oral and intravenous amiodarone therapy to prevent postoperative atrial fibrillation. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. This study addressed the hypothesis that atrium-specific drug delivery through an amiodarone-eluting epicardial patch reduces vulnerability to atrial tachyarrhythmias, whereas ventricular and plasma drug concentrations are minimized. Methods: Right atrial epicardiums of goats were fitted with electrodes and a bilayered patch (poly[ethylene glycol]-based matrix and poly[lactide-co-caprolactone] backing layer) loaded with amiodarone (10 mg per patch, n=10) or without drug (n=6). Electrophysiologic parameters (atrial effective refractory period, conduction time, and rapid atrial response to burst pacing) and amiodarone levels in plasma and tissue were measured during 1 month's follow-up. Results: Epicardial application of amiodarone-eluting patches produced persistently higher drug concentrations in the right atrium than in the left atrium, ventricles, and extracardiac tissues by 2 to 4 orders of magnitude. Atrial effective refractory period and conduction time increased, whereas rapid atrial response inducibility decreased significantly (P
AB - Objective: Clinical studies have demonstrated the efficacy of oral and intravenous amiodarone therapy to prevent postoperative atrial fibrillation. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. This study addressed the hypothesis that atrium-specific drug delivery through an amiodarone-eluting epicardial patch reduces vulnerability to atrial tachyarrhythmias, whereas ventricular and plasma drug concentrations are minimized. Methods: Right atrial epicardiums of goats were fitted with electrodes and a bilayered patch (poly[ethylene glycol]-based matrix and poly[lactide-co-caprolactone] backing layer) loaded with amiodarone (10 mg per patch, n=10) or without drug (n=6). Electrophysiologic parameters (atrial effective refractory period, conduction time, and rapid atrial response to burst pacing) and amiodarone levels in plasma and tissue were measured during 1 month's follow-up. Results: Epicardial application of amiodarone-eluting patches produced persistently higher drug concentrations in the right atrium than in the left atrium, ventricles, and extracardiac tissues by 2 to 4 orders of magnitude. Atrial effective refractory period and conduction time increased, whereas rapid atrial response inducibility decreased significantly (P
U2 - 10.1016/j.jtcvs.2010.01.021
DO - 10.1016/j.jtcvs.2010.01.021
M3 - Article
C2 - 20363485
SN - 0022-5223
VL - 140
SP - 904
EP - 910
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 4
ER -