Shear-activated Nanoparticle Aggregate Lysis Combined With Temporary Stent-bypass to Treat Emergent Large Vessel Occlusions (ELVO)

Introduction: Despite the high effectiveness of stent-retrievers in ELVO, half of the patients remained functionally dependent (mRS≥3) after 90-days. Beyond futile recanalizations, variable endoluminal damage caused by stent-retrievers may contribute to reperfusion injury, and recruit iniflammatory cell infiltration. The goal of this study was to assess a less traumatic endovascular approach in combination with a novel shear activated-nanotherapeutic (SA-NT) that releases r-tPA when exposed to high levels of hemodynamic stress. Hypothesis: SA-NT treatment coupled with temporary endovascular bypass provides high recanalization rates while reducing vascular injury. Methods: a rabbit carotid vessel occlusion model was used. We evaluated angiographic recanalization with stent-bypass alone, intra-arterial delivery of soluble r-tPA alone, or stent-bypass combined with two doses (2 and 20 mg r-tPA) of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy by assessing the level of damage on histology. Results: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared to controls (p=0.0011). SA-NT (20mg) had a higher likelihood of obtaining complete recanalization (mTICI:3) as compared to stent-bypass alone (OR: 65.019,95%CI:[1.77,u003e1000], p=0.0231), intra-arterial r-tPA alone (OR: 65.019, 95% CI [1.77,u003e1000], p=0.0231), or stent-bypass with soluble r-tPA (2 mg) (OR: 18.78, 95%CI [1.28,275.05], p=0.0322) (Figure). Histologically, there was significantly less vascular injury using a stent-bypass as compared to stent-retriever procedure (OR 12.97, 95%CI [8.01,21.02], p Conclusion: Nanoparticle-based thrombolytic therapy combined with stent-bypass achieves high rates of complete (mTICI:3) recanalization. This technology reduces vascular trauma as compared to stent-retriever thrombectomy