Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid—an Experimental Study

  • Andreas Synetos
  • Konstantinos Toutouzas
  • Maria Drakopoulou
  • Iosif Koutagiar
  • George Benetos
  • Rafail Kotronias
  • Nikolaos Anousakis-Vlachochristou
  • George Latsios
  • Antonis Karanasos
  • George Agrogiannis
  • Marinos Metaxas
  • Konstantinos Stathogiannis
  • Aggelos Papanikolaou
  • Alexandros Georgakopoulos
  • Nikoleta Pianou
  • Eleftherios Tsiamis
  • Efstratios Patsouris
  • Apostolos Papalois
  • Dennis Cokkinos
  • Constantinos Anagnostopoulos
  • Dimitrios Tousoulis
Original Article
  • 28 Downloads

Abstract

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20 ± 0.12 vs 1.17 ± 0.78,p = 0.29), while AV calcification progressed in the placebo group (1.22 ± 0.15 vs 1.53 ± 0.23,p = 0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.

Keywords

Bisphosphonates Aortic valve Calcification 

Abbreviations

Aortic valve

AV

Ascending aorta

AA

Aortic valve area

AVA

Positron emission tomography-computed tomography

PET/CT

Mean tissue to background ratios

TBRmean

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andreas Synetos
    • 1
  • Konstantinos Toutouzas
    • 1
  • Maria Drakopoulou
    • 1
  • Iosif Koutagiar
    • 1
  • George Benetos
    • 1
  • Rafail Kotronias
    • 1
  • Nikolaos Anousakis-Vlachochristou
    • 1
  • George Latsios
    • 1
  • Antonis Karanasos
    • 1
  • George Agrogiannis
    • 2
  • Marinos Metaxas
    • 3
  • Konstantinos Stathogiannis
    • 1
  • Aggelos Papanikolaou
    • 1
  • Alexandros Georgakopoulos
    • 3
  • Nikoleta Pianou
    • 3
  • Eleftherios Tsiamis
    • 1
  • Efstratios Patsouris
    • 2
  • Apostolos Papalois
    • 4
  • Dennis Cokkinos
    • 3
  • Constantinos Anagnostopoulos
    • 3
  • Dimitrios Tousoulis
    • 1
  1. 1.First Department of Cardiology, Hippokration HospitalAthens Medical SchoolAthensGreece
  2. 2.Department of PathologyAthens Medical SchoolAthensGreece
  3. 3.Center of Experimental Surgery, Clinical and Translational Research, Biomedical Research FoundationAcademy of AthensAthensGreece
  4. 4.Experimental Research Center ELPENAthensGreece

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