Cardiovascular Drugs and Therapy

, Volume 27, Issue 2, pp 125–132

Liposomal Amiodarone Augments Anti-arrhythmic Effects and Reduces Hemodynamic Adverse Effects in an Ischemia/Reperfusion Rat Model

  • Hiroyuki Takahama
  • Hirokazu Shigematsu
  • Tomohiro Asai
  • Takashi Matsuzaki
  • Shoji Sanada
  • Hai Ying Fu
  • Keiji Okuda
  • Masaki Yamato
  • Hiroshi Asanuma
  • Yoshihiro Asano
  • Masanori Asakura
  • Naoto Oku
  • Issei Komuro
  • Masafumi Kitakaze
  • Tetsuo Minamino
ORIGINAL ARTICLE

DOI: 10.1007/s10557-012-6437-6

Cite this article as:
Takahama, H., Shigematsu, H., Asai, T. et al. Cardiovasc Drugs Ther (2013) 27: 125. doi:10.1007/s10557-012-6437-6

Abstract

Purpose

Although amiodarone is recognized as the most effective anti-arrhythmic drug available, it has negative hemodynamic effects. Nano-sized liposomes can accumulate in and selectively deliver drugs to ischemic/reperfused (I/R) myocardium, which may augment drug effects and reduce side effects. We investigated the effects of liposomal amiodarone on lethal arrhythmias and hemodynamic parameters in an ischemia/reperfusion rat model.

Methods and Results

We prepared liposomal amiodarone (mean diameter: 113 ± 8 nm) by a thin-film method. The left coronary artery of experimental rats was occluded for 5 min followed by reperfusion. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads accumulated in the I/R myocardium. Amiodarone was measurable in samples from the I/R myocardium when liposomal amiodarone, but not amiodarone, was administered. Although the intravenous administration of amiodarone (3 mg/kg) or liposomal amiodarone (3 mg/kg) reduced heart rate and systolic blood pressure compared with saline, the decrease in heart rate or systolic blood pressure caused by liposomal amiodarone was smaller compared with a corresponding dose of free amiodarone. The intravenous administration of liposomal amiodarone (3 mg/kg), but not free amiodarone (3 mg/kg), 5 min before ischemia showed a significantly reduced duration of lethal arrhythmias (18 ± 9 s) and mortality (0 %) during the reperfusion period compared with saline (195 ± 42 s, 71 %, respectively).

Conclusions

Targeting the delivery of liposomal amiodarone to ischemic/reperfused myocardium reduces the mortality due to lethal arrhythmia and the negative hemodynamic changes caused by amiodarone. Nano-size liposomes may be a promising drug delivery system for targeting I/R myocardium with cardioprotective agents.

Keywords

LiposomeAmiodaroneLethal arrhythmiaIschemiaReperfusion

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hiroyuki Takahama
    • 2
    • 5
  • Hirokazu Shigematsu
    • 3
  • Tomohiro Asai
    • 3
  • Takashi Matsuzaki
    • 1
  • Shoji Sanada
    • 1
  • Hai Ying Fu
    • 1
  • Keiji Okuda
    • 1
  • Masaki Yamato
    • 1
  • Hiroshi Asanuma
    • 4
  • Yoshihiro Asano
    • 1
  • Masanori Asakura
    • 2
  • Naoto Oku
    • 3
  • Issei Komuro
    • 1
  • Masafumi Kitakaze
    • 2
  • Tetsuo Minamino
    • 1
  1. 1.Department of Cardiovascular MedicineOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Department of Cardiovascular MedicineNational Cerebral and Cardiovascular CenterSuitaJapan
  3. 3.Department of Medical Biochemistry and Global COEUniversity of Shizuoka Graduate School of Pharmaceutical SciencesShizuokaJapan
  4. 4.Department of Cardiovascular Science and TechnologyKyoto Prefectural University School of MedicineKyotoJapan
  5. 5.Division of Cardiovascular DiseaseMayo ClinicRochesterUSA