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Prolonged Targeting of Ischemic/Reperfused Myocardium by Liposomal Adenosine Augments Cardioprotection in Rats
- Source :
- Journal of the American College of Cardiology. (8):709-717
- Publisher :
- American College of Cardiology Foundation. Published by Elsevier Inc.
-
Abstract
- ObjectivesThe purpose of this study was to investigate whether liposomal adenosine has stronger cardioprotective effects and fewer side effects than free adenosine.BackgroundLiposomes are nanoparticles that can deliver various agents to target tissues and delay degradation of these agents. Liposomes coated with polyethylene glycol (PEG) prolong the residence time of drugs in the blood. Although adenosine reduces the myocardial infarct (MI) size in clinical trials, it also causes hypotension and bradycardia.MethodsWe prepared PEGylated liposomal adenosine (mean diameter 134 ± 21 nm) by the hydration method. In rats, we evaluated the myocardial accumulation of liposomes and MI size at 3 h after 30 min of ischemia followed by reperfusion.ResultsThe electron microscopy and ex vivo bioluminescence imaging showed the specific accumulation of liposomes in ischemic/reperfused myocardium. Investigation of radioisotope-labeled adenosine encapsulated in PEGylated liposomes revealed a prolonged blood residence time. An intravenous infusion of PEGylated liposomal adenosine (450 μg/kg/min) had a weaker effect on blood pressure and heart rate than the corresponding dose of free adenosine. An intravenous infusion of PEGylated liposomal adenosine (450 μg/kg/min) for 10 min from 5 min before the onset of reperfusion significantly reduced MI size (29.5 ± 6.5%) compared with an infusion of saline (53.2 ± 3.5%, p < 0.05). The antagonist of adenosine A1, A2a, A2b, or A3subtype receptor blocked cardioprotection observed in the PEGylated liposomal adenosine-treated group.ConclusionsAn infusion as PEGylated liposomes augmented the cardioprotective effects of adenosine against ischemia/reperfusion injury and reduced its unfavorable hemodynamic effects. Liposomes are promising for developing new treatments for acute MI.
- Subjects :
- Male
Cardiotonic Agents
Vasodilator Agents
medicine.medical_treatment
Ischemia
Blood Pressure
Myocardial Reperfusion Injury
Pharmacology
Fluorescence
Polyethylene Glycols
medicine
Animals
drug delivery system
Rats, Wistar
Infusions, Intravenous
Saline
Cardioprotection
Drug Carriers
Liposome
Dose-Response Relationship, Drug
business.industry
Myocardium
medicine.disease
Adenosine
Rats
myocardial infarction
adenosine
Anesthesia
Liposomes
Circulatory system
liposome
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
Ex vivo
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 07351097
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of the American College of Cardiology
- Accession number :
- edsair.doi.dedup.....f168f9667f37a50728021374fefb31bb
- Full Text :
- https://doi.org/10.1016/j.jacc.2008.11.014