ATP-Loaded Liposomes Effectively Protect the Myocardium in Rabbits with an Acute Experimental Myocardial Infarction
- 256 Downloads
We assessed whether the infusion of ATP-loaded liposomes (ATP-L) can limit the fraction of the irreversibly damaged myocardium in rabbits with an experimental myocardial infarction.
ATP-L, empty liposomes (EL), or Krebs–Henseleit (KH) buffer were administered by intracoronary infusion, followed by 30 min of occlusion and 3 h of reperfusion. Unisperse Blue dye was used to demarcate the net size of the occlusion-induced ischemic zone (area at risk) and nitroblue tetrazolium staining was used to detect the final fraction of the irreversibly damaged myocardium within the total area at risk.
The total size of the area at risk in all experimental animals was approx. 20% wt. of the left ventricle. The final irreversible damage in ATP-L-treated animals was only ca. 30% of the total area at risk as compared with ca. 60% in the group treated with EL (p < 0.009) and ca. 70% in the KH buffer-treated group (p < 0.003).
ATP-L effectively protected the ischemic heart muscle in rabbits with an experimental myocardial infarction as evidenced by a significantly decreased fraction of the irreversibly damaged heart within the total area at risk. ATP-L may provide an effective exogenous source of the ATP in vivo to protect ischemically damaged cells.
Key WordsATP experimental myocardial infarction heart muscle ischemia liposomes mechanical functions rabbits reperfusion
liposomes loaded with ATP
enhanced permeability and retention
unispearse blue dye
This study was supported by the NIH grant RO1 HL55519 to Vladimir P. Torchilin. The authors acknowledge the advice and support by Dr. B.-A. Khaw.
- 4.D. D. Verma, T. S. Levchenko, E. A. Bernstein, and V. P. Torchilin. ATP-loaded liposomes effectively protect mechanical functions of the myocardium from global ischemia in an isolated rat heart model. J. Control. Release In press (2005).Google Scholar
- 5.Lasic, D. D., Papahajopoulos, D. 1998Medical Application of LiposomesElsevierAmsterdam, The NetherlandsGoogle Scholar
- 26.Mixich, F., Mihailescu, S. 1997Liposome microcapsules: an experimental model for drug transport across the Blood–Brain Barrier (BBB)deBoer, B.Sutanto, W. eds. Drug Transport Across the Blood–Brain BarrierHarwood Acad. Publ.Amsterdam201213Google Scholar