Journal
JOURNAL OF CONTROLLED RELEASE
Volume 108, Issue 2-3, Pages 460-471Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2005.08.029
Keywords
isolated rat heart; rabbit myocardial infarction; mechanical functions; ischemia; reperfusion; ATP; liposomes
Funding
- NHLBI NIH HHS [R01 HL055519, R01 HL55519] Funding Source: Medline
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ATP-loaded liposomes (ATP-L) infused into Langendorff-instrumented isolated rat hearts protect the mechanical functions of the myocardium during ischemia/reperfusion. The left ventricular developed pressure (LVDP) at the end of the reperfusion in the ATP-L group recovered to 72% of the baseline (preservation of the systolic function) compared to 26%, 40%, and 51% in the groups treated with Krebs-Henseleit (KH) buffer, empty liposomes (EL), and free ATP (F-ATP), respectively. The ATP-L-treated group also showed a significantly lower left ventricular end diastolic pressure (LVEDP; better preservation of the diastolic function) after ischemia/reperfusion than controls. After incubating the F-ATP and ATP-L with ATPase, the protective effect of the F-ATP was completely eliminated because of ATP degradation, while the protective effect of the ATP-L remained unchanged. Fluorescence microscopy confirmed the accumulation of liposomes in ischemic areas, and the net ATP in the ischemic heart increased with ATP-L. Our results suggest that ATP-L can effectively protect myocardium from ischemic/reperfusion damage. (c) 2005 Elsevier B.V. All rights reserved.
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