Document Detail


Liposomal Amiodarone Augments Anti-arrhythmic Effects and Reduces Hemodynamic Adverse Effects in an Ischemia/Reperfusion Rat Model.
MedLine Citation:
PMID:  23344929     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  -     ISSN:  1573-7241     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, 565-8565, Japan.
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