Evaluation of a new model of hind limb ischemia in rabbits

Objective: Various animal models of critical limb ischemia have been developed in the past. However, there is no animal model that can undergo endovascular treatment, while providing reproducible true critical limb ischemia with arterial ulcers and rest pain. We evaluated the efficacy of a new model of rabbit hindlimb ischemia created through a percutaneous approach using embolization with calibrated particles. Methods: Through a percutaneous transauricular artery approach and selective catheterization of the superficial femoral artery, embolization of distal limb vessels was performed using a mixture of 300- to 500-mm calibrated microparticles (Embosphere, Merit Medical, Salt Lake City, Utah), saline solution, and iodine contrast. Clinical and ultrasound imaging-based blood flow evaluation was performed before embolization and during follow-up. Histologic evaluation was performed at humane killing 14 days after the procedure. Results: The model was successfully created in 10 rabbits (10 limbs). One rabbit died of sudden death at 8 days after the procedure. The nine surviving rabbits developed hind ulcers. All rabbits had a higher pain score in the follow-up compared to baseline value (P <.0001). Blood flow in the saphenous artery decreased significantly after the procedure and later at 14 days follow-up (baseline value 63.4 +/- 31.3 mu L per cardiac cycle vs 32.0 +/- 28.4 mu L per cardiac cycle postprocedure [P =.0013] and 32.0 +/- 28.4 mu L per cardiac cycle at 14 days [P =.0015]). Pathology showed signs of severe limb ischemia in all rabbits with subacute and chronic injury patterns. Conclusions: A rabbit hind limb ischemia model created by percutaneous transauricular distal femoral artery embolization with calibrated particles may overcome some of the limitations of existing animal models. As such, this model could prove useful for assessing therapies designed to improve arterial perfusion and collateral growth. (J Vasc Surg 2018; 68: 849-57.) Clinical Relevance: An in vivo animal model of critical limb ischemia, consisting of surgical excision of the superficial femoral artery, presents limitations to prove the efficacy of therapies designed to improve arterial perfusion and collateral growth, such as stem cell treatment. The natural propensity of collaterals to overcome the proximal arterial occlusion usually precludes the onset of significant critical limb ischemia. We evaluated the efficacy of a new model of rabbit hindlimb ischemia created through a percutaneous approach using embolization of distal hind vessels by calibrated particles that may overcome some of limitations of existing animal models and prove useful for future studies.