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A novel murine model of stenting
  1. J Chamberlain1,
  2. M Wheatcroft1,
  3. N Arnold1,
  4. S Francis1,
  5. H Lupton2,
  6. J Gunn1
  1. 1University of Sheffield, Sheffield, UK
  2. 2Brivant Medical Engineering, Galway, Ireland

Abstract

Introduction Animal models of stenting are mostly limited to larger animals that do not have from atherosclerosis. Conversely, genetically modified mice are susceptible to atherosclerosis. Until recently, however, size constraints have prevented stent studies in mice. A recent balloon expandable arterial stent graft model in the mouse has proved successful, although it requires vessel transplantation. We have developed a simple, direct model of murine stenting that deploys the stent in situ.

Methods We designed a miniature, self-expanding, nitinol wire coil stent for use in the mouse abdominal aorta. Mice were pretreated for 48 h with aspirin and clopidogrel, general anaesthesia was induced and analgesic given. A metal stent sheath was advanced via a femoral arteriotomy into the abdominal aorta and the stent was deployed by retracting the sheath over a pusher wire. The femoral artery was ligated and the wound closed. Double antiplatelet therapy was continued postoperatively until harvest at 1, 3, 7 and 28 days, when the animals were killed and perfusion fixed. Stented sections were embedded in glycol methacrylate resin and transverse sections made using a diamond-tipped saw. Morphometric analysis was performed on H&E stained sections.

Results 59 mice underwent the stenting procedure, of which 37 recovered postoperatively. Most (68%) of the failed procedures occurred early in the development of the technique, showing a steep learning curve for the procedure. Of the “successful” procedures, 92% resulted in the recovery of a stented aorta. All arteries were patent upon harvest. Inflammatory cells were seen in the adventitia and around the stent strut at 1 day (see fig (A)) and up to 3 days post-stenting. At 3 days an early neointima was present (B). At 7 days, a lining of endothelial cells was observed over the stent strut (C). At 28 days there was a mature neointima (D).

Conclusions This is the first description of a successful model of murine in-situ stenting, using a stent specifically tailored for use in small thin-walled arteries. The procedure can be undertaken by a single operator without the need for an advanced level of microsurgical skill and is reliable and reproducible. This model may be useful in the future of stent research, allowing research into molecular mechanisms via the use of transgenic animals and providing a convenient platform for testing drug-eluting stent coatings.

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