Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias
Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias
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DOI：
10.1016/j.ijcard.2010.02.014
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发表时间：
2011-06-16
影响因子：
3.5
通讯作者：
Maessen, Jos G.
中科院分区：
文献类型：
--
作者：
Bolderman, Robert W.;Hermans, J. J. Rob;Maessen, Jos G.
背景：胺碘酮是目前维持窦性心律最有效的抗心律失常药物。然而，由于严重的心外不良反应，预防性胺碘酮治疗仅适用于术后房颤（AF）高危患者。我们假设，心外膜应用胺碘酮释放水凝胶将产生治疗心肌药物浓度，而全身水平将保持low.Methods：山羊右心房心外膜贴片电极。将含胺碘酮（1 mg/ kg bw）（n=10）或不含药物（n=6）的聚（乙二醇）基水凝胶应用于右心房心外膜。在清醒山羊中评估心房有效不应期（AERP）、传导时间和心房对短阵起搏的反应（快速心房反应，RAR），持续28天。心肌，血浆和心外组织胺碘酮浓度进行了分析，通过高效液相色谱法。结果：胺碘酮负载水凝胶产生治疗药物浓度在右心房21天后应用。在此期间，与无药物水凝胶治疗的动物相比，AERP和传导时间延长，而RAR诱导减少（P <0.05）。右心房中胺碘酮的平均浓度比其他心腔高1个数量级，比心外组织高2个数量级。血浆胺碘酮水平保持低于检测限（b10 ng/ mL）在28天follow-up.Conclusions：心外膜应用胺碘酮释放水凝胶减少心房脆弱性快速心律失常长达3周，而心外药物水平仍然很低。因此，胺碘酮释放水凝胶可在心脏手术期间应用，以预防术后AF，心外不良副作用的风险最小。c 2010爱思唯尔爱尔兰有限公司保留所有权利。
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 Elsevier Ireland Ltd. All rights reserved.