Korean Circ J.  2013 Nov;43(11):713-722. 10.4070/kcj.2013.43.11.713.

Development of a Rabbit Model for a Preclinical Comparison of Coronary Stent Types In-Vivo

• Lee JM
• Lee J
• Jeong H
• Choe WS
• Seo WW
• Lim WH
• Kim YC
• Hur J
• Lee SE
• Yang HM
• Cho HJ
• Kim HS

• KMID: 2224801
• DOI: http://doi.org/10.4070/kcj.2013.43.11.713

Abstract

Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.

Keyword

Prosthesis and implants; Stents; Model, animal; NZW rabbits

MeSH Terms

Animals
Body Weight
Coronary Vessels
Humans
Iliac Artery
Models, Animal
Rabbits
Research Personnel
Stents*
Tissue and Organ Harvesting

Figure

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  Fig. 1 Dissection of the right carotid artery for vascular access. Before the entire procedure commences, the midline of the rabbit should be marked (A). After local anesthesia with lidocaine solution (B), a lateral incision was made 0.5-1 cm from the midline (C). The internal jugular vein was exposed after the subcutaneous fascia was dissected (D and E, arrowhead). The arrow indicates the imaginary dissection plane to expose the carotid artery (E). The right carotid artery and vagus nerve were exposed through a dissection of the medial side of the internal jugular vein (F, arrowhead).

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  Fig. 2 Mobilization of the carotid artery. The carotid artery was mobilized using blunt dissection is (A and B). The distal vessel was ligated to dilate the carotid artery and make for an easy puncture (C and D). Two loose sutures were placed around the proximal vessel (E and F).

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  Fig. 3 Puncture technique and insertion of the introducer sheath. The carotid artery was punctured with 22 G angiosheath with the bevel facing downward (A). During the removal of the angiosheath, the proximal suture was pulled upward to prevent arterial bleeding (C, arrowhead). The 4 Fr introducer sheath was gently advanced through the 0.014 inch coronary guide wire into the punctured arterial wall (D and E), and subsequently secured with a tagging suture (F).

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  Fig. 4 Stent implantation and angiograms. Once the introducer sheath was inserted, heparin was injected intra-arterially through the introducer sheath to prevent thrombus formation. The 0.014 inch coronary guide wire was advanced from the carotid artery into the distal descending aorta (A). The guide wire never advanced above the level of the distal femur, to prevent perforation of the distal iliac artery (B and C). The final angiogram shows the successful implantation of stents in both iliac arteries with a stent-to-artery-size ratio range of 1.1-1.2 (D).

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  Fig. 5 Assessment of the early re-endothelialization and neointimal area. Scanning the electron microscopic image of a 72-hour harvest sample of anti VE-cadherin antibody coated stents (A). The surface of the bare metal stent and anti VE-cadherin antibody coated stents are shown 3 days after implantation (B and D, respectively). The covered stent surface was measured and quantitatively analyzed (C). A representative hematoxylin and eosin stained sample harvested 6 weeks after implantation (E). The neointimal area was measured by subtracting area 2 (luminal area) from area 1 (internal elastic membrane area) (F).

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