局部应用胺碘酮可降解盘治疗心房颤动。

Topical application of a biodegradable disc with amiodarone for atrial fibrillation.

机构信息

Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Ann Thorac Surg. 2011 Mar;91(3):734-9. doi: 10.1016/j.athoracsur.2010.10.022.

DOI:10.1016/j.athoracsur.2010.10.022

PMID:21352989

Abstract

BACKGROUND

Amiodarone is a potent anti-atrial fibrillation (AF) agent; however, its systemic administration induces serious side effects such as interstitial pneumonia. To avoid such effects, we developed a local sustained-release system for amiodarone.

METHODS

A biodegradable, cross-linkable dextran disc was developed as a sustained-release carrier for amiodarone. Under general anesthesia, Japanese white rabbits underwent median sternotomy and the biodegradable disc with or without amiodarone (30 mg) was implanted onto the surface of the right atrium. Three days after implantation, we measured tissue amiodarone concentrations (n = 5), the AF threshold, and the atrial effective refractory period of the left atrium by using the Langendorff apparatus. The incidences of induced AF evoked by rapid pacing were measured and compared.

RESULTS

The right atrial concentration of amiodarone was far higher than that in the lungs, ventricles, or other organs (p < 0.01). The blood concentration of amiodarone was below detectable levels. The amiodarone biodegradable disc significantly increased the AF threshold (amiodarone group, 6.9 ± 4.6 mA versus control group, 0.5 ± 0.6 mA; p < 0.01) and the effective refractory period (amiodarone group, 53.9 ± 8.9 milliseconds versus control group, 43.9 ± 9.5 milliseconds; p = 0.035) of the left atrium, indicating the electrophysiologic effect of the amiodarone biodegradable disc on the left atrium. Further, the amiodarone group was significantly less likely to experience AF, as compared with the control group (p < 0.01).

CONCLUSIONS

This approach may be a less invasive and effective therapeutic option for preventing postoperative AF.

摘要

背景

胺碘酮是一种有效的抗心房颤动（AF）药物；然而，其全身给药会引起严重的副作用，如间质性肺炎。为了避免这种影响，我们开发了一种胺碘酮的局部缓释系统。

方法

我们开发了一种可生物降解的、可交联的葡聚糖盘作为胺碘酮的缓释载体。在全身麻醉下，日本白兔行正中胸骨切开术，将含有或不含有胺碘酮（30mg）的可生物降解盘植入右心房表面。植入后 3 天，我们使用 Langendorff 装置测量组织胺碘酮浓度（n=5）、AF 阈值和左心房的有效不应期。测量并比较了快速起搏诱发 AF 的发生率。

结果

右心房的胺碘酮浓度明显高于肺部、心室或其他器官（p<0.01）。血液中的胺碘酮浓度低于检测水平。胺碘酮可生物降解盘显著提高 AF 阈值（胺碘酮组 6.9±4.6mA，对照组 0.5±0.6mA；p<0.01）和左心房的有效不应期（胺碘酮组 53.9±8.9ms，对照组 43.9±9.5ms；p=0.035），表明胺碘酮可生物降解盘对左心房的电生理作用。此外，与对照组相比，胺碘酮组发生 AF 的可能性明显降低（p<0.01）。