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Protective Effect of Coenzyme Q10-loaded Liposomes on the Myocardium in Rabbits with an Acute Experimental Myocardial Infarction

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Abstract

Purpose

We assessed whether the infusion of Coenzyme Q10-loaded liposomes (CoQ10-L) in rabbits with an experimental myocardial infarction can result in increased intracellular delivery of CoQ10 and thus limit the fraction of the irreversibly damaged myocardium.

Methods

CoQ10-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”) while 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 (LV). The final irreversible damage in CoQ10-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 < 0.006) and ca. 70% in the KH buffer-treated group (p < 0.001).

Conclusions

CoQ10-L effectively protected the ischemic heart muscle by enhancing the intracellular delivery of CoQ10 in hypoxic cardiocytes 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. CoQ10-L may provide an effective exogenous source of the CoQ10 in vivo to protect ischemic cells

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Abbreviations

Ch:

Cholesterol

CoQ10-L:

Coenzyme Q10 liposomes

DD:

Detergent dialysis

DOTAP:

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

ECG:

Electrocardiogram

ED:

Ethanol dissolution

EL:

Empty liposomes

EPR:

Enhanced permeability and retention

KH:

Kreb sHenseleit

LDL:

Low-density lipoprotein

LFH:

Lipid film hydration

LV:

Left ventricle

NBT:

Nitro blue tetrazolium

PC:

Egg phosphatidylcholine

PEG-PE:

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

REV:

Reverse phase evaporation

USB:

Unispearse blue dye

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Acknowledgement

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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Author notes

  1. Daya D. Verma

    Present address: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey, 07936, USA

Authors and Affiliations

  1. Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA

    Daya D. Verma, William C. Hartner, Vineet Thakkar, Tatyana S. Levchenko & Vladimir P. Torchilin

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  1. Daya D. Verma
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  2. William C. Hartner
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  3. Vineet Thakkar
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Correspondence to Vladimir P. Torchilin.

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Verma, D.D., Hartner, W.C., Thakkar, V. et al. Protective Effect of Coenzyme Q10-loaded Liposomes on the Myocardium in Rabbits with an Acute Experimental Myocardial Infarction. Pharm Res 24, 2131–2137 (2007). https://doi.org/10.1007/s11095-007-9334-0

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