Translating Thrombolytic Efficacy of Von Willebrand Factor Aptamer Inhibition From a Small to Large Animal Model of Carotid Occlusion

Introduction: While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, recanalization is only achieved in 25-50% of patients. Previous work demonstrated that aptamer inhibition of Von Willebrand Factor (VWF) effectively restores reperfusion following FeCl3-induced murine carotid artery occlusion (Figure 1A). Hypothesis: We tested the hypothesis that: 1) FeCl3-induced arterial occlusion model will translate into a large animal and 2) VWF aptamer will restore recanalization and reperfusion better than rTPA. Methods: Adult male and female beagles were anesthetized and intubated. The right carotid artery was exposed, and carotid flow was monitored throughout the study using a Doppler flow probe. Thrombus was induced with 50% FeCl3for 15 minutes and stabilized for 45 minutes followed by IV infusion of vehicle (n=6), rTPA (n=5) or VWF aptamer (n=5). Angiography at baseline, occlusion, and at 120 minutes recorded carotid patency while blood draws assessed platelet inhib...