Abstract 3836: Efficacy And Safety Evaluation Of Endovascular Revascularization Devices In The A Rabbit CCA Occlusive Model
Background: Intra-arterial recanalization strategies targeting acute ischemic stroke (AIS) are a focus of increased interest, since their use results in a faster and a higher grade of recanalization. We evaluated different treatment strategies in a dedicated rabbit CCA model of thromboembolic occlusion. The response to Alteplase in rabbits is similar to humans; making this model ideal for thrombolytic evaluation.
Method: New Zealand White rabbits were anesthetized, the CCA was exposed and a luminal stenosis created bilaterally with 3-0 silk suture. Allogenic clot was injected through a 6F catheter, which lodged consistently at the site of the stenosis. Allowing 45 minutes for clot-vessel wall interaction, the stenosis was released. The clot adhered to the vessel wall and did not migrate distally. The occlusion was treated with either intra-arterial Alteplase (n=4), balloon angioplasty (n=3), balloon infusion wire (NIT Therapeutics, PA; n=3) which in its embodiment mechanically disrupts and adjuvantly delivers Alteplase within the clot or partial stent deployment as a temporary bypass with (n=2) and without Alteplase (n=5). The control vessel (n=4) received no treatment. The primary efficacy endpoint was the final thrombolysis in cerebral infarction (TICI) score. The primary safety endpoint was the vascular safety of the device, which was assessed on luminal scanning electron microscopy (SEM) and hematoxylin and eosin staining.
Results: Thromboembolic occlusion was created successfully with TICI 0 flow at the CCA in all animals. Partial stent deployment resulted in transient revascularization, however on resheathing, the vessel reoccluded. Use of partial stent deployment with adjuvant Alteplase resulted in revascularization in the high dose (4mg) group, however it failed to recanalize when using a lower (2mg) dose. Use of balloon angioplasty alone or intra-arterial Alteplase alone often failed to revascularize the vessel. The use of the balloon infusion wire resulted in a higher grade of recanalization (TICI 2B) consistently at a lower dose of Alteplase. Histomorphometric and SEM data revealed an acceptable level of disruption for endovascular devices, with endothelial denudation and exposure of the internal elastic lamina.
Conclusion: With incorporation of newer endovascular treatment strategies to treat AIS, it is imperative to test their safety and efficacy in valid preclinical models, which simulates the thrombolytic and mechanical device- clot interaction as experienced in humans.
- © 2012 by American Heart Association, Inc.