title: Topical application of a biodegradable disc with amiodarone for atrial fibrillation.
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.
authors.affiliation: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Takeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.forename: Naritatu
authors.initials: N
authors.lastname: Saito
authors.forename: Kyokun
authors.initials: K
authors.lastname: Uehara
authors.forename: Kenji
authors.initials: K
authors.lastname: Minakata
authors.forename: Senri
authors.initials: S
authors.lastname: Miwa
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakajima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Suong-Hyu
authors.initials: SH
authors.lastname: Hyon
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
mesh_terms: D020341:Absorbable Implants; D000287:Administration, Topical; D000638:Amiodarone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D003911:Dextrans; D000638:Amiodarone