A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

Gounis, Matthew J.; Nogueira, Raul G; Mehra, Manik; Chueh, Juyu; Wakhloo, Ajay K.

doi:10.1136/neurintsurg-2012-010435

Cited by 17 publications

(14 citation statements)

References 20 publications

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“…In our model, because of the extensive network of collaterals within the circle of Willis and MCA branches, we measured reperfusion with the TICI score rather than recording changes in pressure and flow gradients. Although recanalization scales can be applied to thrombectomy experiments conducted in animal models, high costs associated with such experiments and differences in anatomy are potential limiting factors 15 16…”

Section: Discussionmentioning

confidence: 99%

Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

Mokin

Ionita

Nagesh

et al. 2014

J NeuroIntervent Surg

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Background Artificial stroke models can be used for testing various thrombectomy devices. Objective To determine the value of combined stentriever–aspiration thrombectomy compared with the stentriever-alone approach. Methods We designed an in vitro model of the intracranial circulation with a focus on the middle cerebral artery (MCA) that closely resembles the human intracranial circulation. After introducing fresh clot in the MCA, we used conventional biplane angiography and microangiographic fluoroscopy to compare recanalization rates and occurrence of emboli in new, unaffected territory for thrombectomy approaches in which a stentriever (Solitaire flow restoration stentriever, Covidien) was used alone or in combination with continuous manual aspiration through a Navien catheter (Covidien). Results In a total of 22 experiments (11 for each approach), successful clot delivery to the MCA was achieved in all cases. Successful angiographic recanalization (thrombolysis in cerebral infarction score of 2b–3) was achieved more frequently with the combined stentriever–aspiration approach than with the stentriever-alone approach (in 10 vs 4 experiments, p=0.023). Emboli in new territory occurred in three experiments with the stentriever-alone approach, and none were seen with the combined approach (p=0.21). Conclusions The combined stentriever–aspiration approach to thrombectomy leads to better angiographic recanalization rates than use of the stentriever alone. Further experiments are needed to test the value of balloon-guide catheters and aspiration performed using other types of catheters and modes of aspiration.

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Section: Discussionmentioning

confidence: 99%

Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

Mokin

Ionita

Nagesh

et al. 2014

J NeuroIntervent Surg

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“…4 We found that vasospasm occurred in 100% of the swine subjects, to at least some extent on all stent retriever passes. Vasodilators (both verapamil and nitroglycerin) ultimately helped to resolve this.…”

Section: Procedure-related Vasospasmmentioning

confidence: 99%

“…Others have popularized rabbit models, which more closely mirror human responses to thrombolytics, but involve smaller rabbit blood vessels. 4,7 The swine model, as used by many others, allows for easy translation of skills from the model to patients, based on similar size and vasculature. After insertion of the femoral sheath via cutdown, the procedure was otherwise a high-fidelity replication of the procedural environment in stroke intervention.…”

Section: Discussionmentioning

confidence: 99%

Development of a recalcitrant, large clot burden, bifurcation occlusion model for mechanical thrombectomy

Srinivasan¹,

Chen

Camstra³

et al. 2017

FOC

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OBJECTIVE Stroke is a major cause of disability and death in adults. Several large randomized clinical trials have shown the significant benefit of mechanical thrombectomy with modern stent retrievers in the treatment of large-vessel occlusions. However, large clots located at bifurcations remain challenging to treat. An in vivo model of these recalcitrant clots needs to be developed to test future generations of devices. METHODS Autologous blood was drawn from anesthetized swine via a femoral sheath. Blood was then mixed with thrombin, calcium chloride, and saline, and injected into silicone tubing to form cylindrical clots in the standard fashion. Matured clots were then delivered in an unfragmented fashion directly into the distal extracranial vasculature, at branch points where vessel sizes mimic the human middle cerebral artery, by using Penumbra aspiration tubing and the Penumbra ACE68 reperfusion catheter. RESULTS A total of 5 adult swine were used to develop the model. The techniques evolved during experiments in the first 3 animals, and the last 2 were used to establish the final model. In these 2 swine, a total of 8 autologous clots, 15–20 mm, were injected directly into 8 distal extracranial vessels at branch points to mimic a bifurcation occlusion in a human. All clots were delivered directly at a distal bifurcation or trifurcation in an unfragmented fashion to cause an occlusion. Ten revascularization attempts were made, and none of the branch-point occlusions were fully revascularized on the first attempt. CONCLUSIONS Using novel large-bore distal access catheters, large unfragmented clots can be delivered into distal extracranial vessels in a swine occlusion model. The model mimics the clinical situation of a recalcitrant bifurcation occlusion and will be valuable in the study of next-generation stroke devices and in training settings.

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“…21 Briefly, autologous, whole arterial blood was combined with bovine thrombin (2.5 U/mL blood) and coagulated in a 10 mm silicone tube and then allowed to age for 3 hours in normal saline at room temperature; clots with a 2.7 mm diameter were used for the creation of vascular occlusion. A cut down to the femoral artery was performed for placement of a 6F hemostatic introducer using a modified Seldinger technique.…”

Section: Methodsmentioning

confidence: 99%

“…In this animal study, we used a previously published rabbit vascular occlusion model developed to study new endovascular devices coupled with thrombolysis. 21 We assessed the combination of the TEB technique with SA-NT-targeted IA r-tPA delivery in this large vessel occlusion model. Our intention was to compare this novel technique to various control groups with particular attention to its efficacy and safety.…”

Section: December 2015mentioning

confidence: 99%

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

Marosfői

Korin

Gounis

et al. 2015

Stroke

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T he majority of the patients having an emergent large vessel occlusion (ELVO) may develop severe and permanent neurological morbidity or death without urgent and successful treatment. Recently published randomized clinical trials have all shown that intra-arterial (IA) treatments in combination with intravenous recombinant tissuetype plasminogen activator (r-tPA) when indicated leads to improved clinical outcomes as compared with standard medical therapy alone. [1][2][3][4] Compared with prior randomized trials that showed no benefit for IA treatment, 5-7 most patients enrolled in these studies received stent-retriever mechanical thrombectomy (MT) that resulted in higher rates of modified thrombolysis in cerebral infarction score (mTICI) 2b or 3 recanalization. Despite high rates of successful recanalization, nearly half of the patients remained functionally dependent (mRS≥3) after 90 days.Background and Purpose-The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shearactivated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. Methods-A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. Results-Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1. 28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). Conclusions-A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy. 14 This observation is supported by results of histopathologic exams from animal studies, where extensive endothelial damage was observed after stent retriever usage. [15][16][17] Focal denudation of the vascular endothelium results in exposure of a hi...

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A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

Cited by 17 publications

References 20 publications

Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

Primary stentriever versus combined stentriever plus aspiration thrombectomy approaches: in vitro stroke model comparison

Development of a recalcitrant, large clot burden, bifurcation occlusion model for mechanical thrombectomy

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

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