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ATP-Loaded Liposomes Effectively Protect the Myocardium in Rabbits with an Acute Experimental Myocardial Infarction

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Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Abbreviations

ATP:

adenosine-5′-triphosphate

ATPase:

adenosine-5′-triphosphatase

ATP-L:

liposomes loaded with ATP

DOTAP:

1,2-dioleoyl-3-trimethyl-ammonium-propane

EL:

empty liposomes

EPR:

enhanced permeability and retention

KH:

Krebs–Henseleit

NBT:

nitroblue tetrazolium

PEG-PE:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]

USB:

unispearse blue dye

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA

    Daya D. Verma, William C. Hartner, Tatayana S. Levchenko, Eugene A. Bernstein & Vladimir P. Torchilin

Authors
  1. Daya D. Verma
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  2. William C. Hartner
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  3. Tatayana S. Levchenko
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  4. Eugene A. Bernstein
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  5. Vladimir P. Torchilin
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Corresponding author

Correspondence to Vladimir P. Torchilin.

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Verma, D.D., Hartner, W.C., Levchenko, T.S. et al. ATP-Loaded Liposomes Effectively Protect the Myocardium in Rabbits with an Acute Experimental Myocardial Infarction. Pharm Res 22, 2115–2120 (2005). https://doi.org/10.1007/s11095-005-8354-x

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  • DOI: https://doi.org/10.1007/s11095-005-8354-x

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