In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
Abstract:
Background Liposome is a nano-size particle that can delay the drug degradation and induce the drug to the specific tissues including ischemia/reperfused myocardium. Coating liposome with polyethylene-glycol (PEG) prolongs the residence time in the blood stream. Although adenosine reduces myocardial infarct size in clinical trials, its half-time is extremely short and a high-dose of adenosine administration causes both hypotension and bradycardia. In this study, we investigated whether PEGylated liposomal adenosine minimizes systemic hemodynamic effects of adenosine and maximize cardioprotective effects against ischemia/reperfusion injury. Methods and Results We obtained PEGylated liposomal adenosine (average diameter: 126.2+/−42.9 nm) by the remote loading method. In rats, the intravenous administration of free adenosine (450 μg/kg/min for 10 minutes) decreased mean blood pressure and heart rate by 22.7% and 15.4% compared with the baseline, respectively. PEGylated liposomal adenosine at the same dose did not significantly change either mean blood pressure or heart rate compared with the baseline. Next, we produced myocardial infarction (MI) in male rats by 30-minutes of ligation of the left anterior descending coronary artery followed by reperfusion. We evaluated the accumulation of liposome in the hearts and infarct size 72 hours after the MI. Fluorescence microscopy revealed the accumulation of fluorescent-labeled PEGylated liposomes in ischemic, but not non-ischemic area. PEGylated liposomal adenosine (450 μg/kg/min), free adenosine (450 μg/kg/min) or free-PEGylated liposome was intravenously administered for 10 minutes starting 5 minutes before the onset of reperfusion. PEGylated liposomal adenosine significantly (p 〈 0.05 each) reduced infarct size (11.4±3.1 %) compared with free adenosine (21.7±3.0%) or free PEGylated liposome (23.6±2.2%). Conculusion PEGylated liposomal adenosine attenuated the systemic hemodynamic effects of adenosine and augmented cardioprotection against ischemia/repefusion injury. Nano-size PEGylated liposomal adenosine is a promising candidate for the adjunctive therapy for AMI.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.116.suppl_16.II_97-a
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2007
detail.hit.zdb_id:
1466401-X
