Rabbit model of in-stent restenosis after percutaneous transluminal intervention

In-stent restenosis, atherosclerosis, rabbit, high fat diet
Figure 1: Stained vessel section with moderate in-stent restenosis, Movat-Pentachrome staining, magnification: 4x

Species

Rabbit (New Zealand White)

Field of application:

Atherosclerosis is alimentary induced by feeding a high fat diet for six weeks. Stent implantation is performed two weeks later. Therapy options comprise oral or parenteral drugs as well as (coated) stents (DES). After 28 days, the animals are sacrificed and neointimal hyperplasia is quantified. The degree of restenosis of a treated group is compared to respective controls.

The model can be used for the following fields of application:

  • Pharmacodynamics and pharmacokinetics in the rabbit (at different time points during high fat diet)
  • Therapeutic efficiency of novel orally or parenterally available small molecules
  • Therapeutic efficiency of novel drug eluting stents or balloon catheters
  • Proof of concept

Endpoints/Outcome parameter

  • Cholesterol and LDL concentration in serum (in vivo)
  • Vessel morphometry (area of neointima, media, neointima /media ratio, remaining lumen, % stenosis, ex vivo)
  • Inflammatory parameters (new injury score, inflammation score, endothelialisation score; ex vivo)
  • Gene expression and enzyme activity in the stented vessel segments (ex vivo)

Readout parameter

  • Morphometry
  • Scores
  • RT-PCR
  • Histology (various histological stainings)

Quality management and validation

  • Controls
  • Randomisation
  • Allocation concealment after stent implantation
  • Blinded data collection and analysis
  • Internal quality management

Weblink(s)

https://www.izi.fraunhofer.de/de/departments/halle-location/department-of-drug-design-and-target-validation/molecular-biotechnology.html#tabpanel-2

References

  • Ribichini F, Joner M, Ferrero V, Finn AV, Crimins J, Nakazawa G et al. Effects of Oral Prednisone After Stenting in a Rabbit Model of Established Atherosclerosis. J Am Coll Cardiol. 2007;50(2):176-85.

  • Langheinrich AC, Zoerb C, Jajima J, Lommel D, Walker G, Mueller K et al. Quantification of In-Stent Restenosis Parameters in Rabbits by Micro-CT. Rofo Fortschr Geb Rontgenstr N. 2005; 177(04):501–6.