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

Authors

  • Hiroyuki Takahama
    • Department of Cardiovascular MedicineNational Cerebral and Cardiovascular Center
    • Division of Cardiovascular DiseaseMayo Clinic
  • Hirokazu Shigematsu
    • Department of Medical Biochemistry and Global COEUniversity of Shizuoka Graduate School of Pharmaceutical Sciences
  • Tomohiro Asai
    • Department of Medical Biochemistry and Global COEUniversity of Shizuoka Graduate School of Pharmaceutical Sciences
  • Takashi Matsuzaki
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Shoji Sanada
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Hai Ying Fu
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Keiji Okuda
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Masaki Yamato
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Hiroshi Asanuma
    • Department of Cardiovascular Science and TechnologyKyoto Prefectural University School of Medicine
  • Yoshihiro Asano
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Masanori Asakura
    • Department of Cardiovascular MedicineNational Cerebral and Cardiovascular Center
  • Naoto Oku
    • Department of Medical Biochemistry and Global COEUniversity of Shizuoka Graduate School of Pharmaceutical Sciences
  • Issei Komuro
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
  • Masafumi Kitakaze
    • Department of Cardiovascular MedicineNational Cerebral and Cardiovascular Center
    • Department of Cardiovascular MedicineOsaka University Graduate School of Medicine
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