ATP-loaded liposomes effectively protect mechanical functions of the myocardium from global ischemia in an isolated rat heart model.
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.
Verma
D D
DD
Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
Levchenko
T S
TS
Bernstein
E A
EA
Torchilin
V P
VP
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004337:Drug Carriers; D004563:Electrochemistry; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008081:Liposomes; D008856:Microscopy, Fluorescence; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000473:pathology* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases