Abstract 1122‐000073: Influence of Catheter Tip Position and Aspiration Technique on ADAPT Revascularization Success with Various Catheters

Author(s):  
Seán T Fitzgerald ◽  
Liam Mullins ◽  
Kevin Connolly ◽  
John Thornton ◽  
Raul G Nogueira

Introduction : Previous studies demonstrated that both the location of the distal access catheter tip and angle of aspiration have a significant impact on revascularization outcomes 1,2 . A direct aspiration First‐Pass technique (ADAPT) with large‐bore aspiration catheters has emerged as a fast, safe, and effective thrombectomy technique. Maximizing the catheter‐to‐vessel size has previously been shown to enhance distal flow control resulting in improved in‐vitro revascularization rates for aspiration thrombectomy 3 . However, physicians differ in their preference for aspiration catheter tip placement, typically either positioning the catheter tip at the ‘face’ of the clot or advancing the catheter tip into the clot to engage it. We hypothesize that sizing the aspiration catheter outer diameter (OD) to the inner diameter (ID) of the vessel and embedding the catheter tip in the clot may result in ‘pinning’ fragments of clot between the catheter and vessel wall, thereby negatively affecting revascularization outcomes. Withdrawal of the aspiration catheter under continuous aspiration may mitigate this effect. We investigate the influence of catheter tip position and aspiration technique on ADAPT revascularization success with various sizes of aspiration catheters. Methods : Two clot analogues phenotypes (RBC‐Rich and Fibrin/Platelet‐Rich) were created from human blood and used to form occlusions in an In‐vitro thrombectomy model as previously described 4 . Two catheter tip positions and three techniques were investigated; 1). Catheter tip proximal to the face of the clot followed by conventional aspiration, 2). Catheter tip ‘embedded’ into the clot followed by conventional aspiration, and 3). Catheter tip ‘embedded’ into the clot followed by conventional aspiration and aspiration on catheter withdrawal even if clot ingestion occurred. Two aspiration catheters were investigated; Millipede 088’’ (Perfuze Ltd) and SOFIA Plus (Terumo). Multiple replicates of each test were performed. Endpoints were First‐Pass Effect and procedural‐related distal emboli from 200–1000µm. Results : Maximizing the catheter‐to‐vessel size increases success of the ADAPT approach when the tip is located proximal to the clot face (Fig 1 A&B); Millipede 088 achieves a higher First‐Pass Effect rate than SOFIA Plus. Sizing the catheter‐to‐vessel and embedding the catheter tip into the clot (Figure 1C) results in ‘pinning’ of clot fragments between the catheter and vessel wall (Figure 1D) resulting in lower rates of First‐Pass Effect. Withdrawing the catheter under continuous aspiration increases the success of the embedding method by capturing ‘pinned’ fragments. Conclusions : The position of the aspiration catheter tip and aspiration technique used both influence the success of ADAPT procedures. Sizing the catheter‐to‐vessel results in improved revascularization. However, embedding the tip into the clot when the vessel is similar in ID to the catheter OD may reduce First‐Pass Effect rates. To optimize the rates of First‐Pass Effect, aspiration catheters may be positioned at the proximal face of the clot or retracted under continuous aspiration if wedged into the clot.

2021 ◽  
pp. neurintsurg-2021-017487
Author(s):  
Jiahui Li ◽  
Oscar Castaño ◽  
Alejandro Tomasello ◽  
Marta de Dios Lascuevas ◽  
Pere Canals ◽  
...  

BackgroundA direct aspiration first pass thrombectomy (ADAPT) is a fast-growing technique for which a broad catalog of catheters that provide a wide range of aspiration forces can be used. We aimed to characterize different catheters' aspiration performance on stiff clots in an in vitro vascular model. We hypothesized that labeled catheter inner diameter (labeled-ID) is not the only parameter that affects the aspiration force (asp-F) and that thrombus–catheter tip interaction and distensibility also play a major role.MethodsWe designed an experimental setup consisting of a 3D-printed carotid artery immersed in a water deposit. We measured asp-F and distensibility of catheter tips when performing ADAPT on a stiff clot analog larger than catheter labeled-ID. Correlations between asp-F, catheter ID, and tip distensibility were statistically assessed.ResultsExperimental asp-F and catheter labeled-ID were correlated (r=0.9601; P<0.01). The relative difference between experimental and theoretical asp-F (obtained by the product of the tip’s section area by the vacuum pressure) correlated with tip’s distensibility (r=0.9050; P<0.01), evidencing that ADAPT performance is highly influenced by catheter tip shape-adaptability to the clot and that the effective ID (eff-ID) may differ from the labeled-ID specified by manufacturers. Eff-ID showed the highest correlation with experimental asp-F (r=0.9944; P<0.01), confirming that eff-ID rather than labeled-ID should be considered to better estimate the device efficiency.ConclusionsCatheter tip distensibility can induce a significant impact on ADAPT performance when retrieving a stiff clot larger than the device ID. Our findings might contribute to optimizing thrombectomy strategies and the design of novel aspiration catheters.


2020 ◽  
Vol 11 ◽  
Author(s):  
You Gao ◽  
Chunmiao Yang ◽  
Lingchao Wang ◽  
Yanan Xiang ◽  
Wenpeng Zhang ◽  
...  

YL-IPA08, exerting rapid antidepressant-like and anxiolytic-like effects on behaviors by translocator protein (TSPO) mediation, is a novel compound that has been discovered and developed at our institute. Fit-for-purpose pharmacokinetic properties is urgently needed to be discovered as early as possible for a new compound. YL-IPA08 exhibited low bioavailability (∼6%) during the preliminary pharmacokinetics study in rats after oral administration. Our aim was to determine how metabolic disposition by microsomal P450 enzymes in liver and intestine limited YL-IPA08’s bioavailability and further affected brain penetration to the target. Studies of in vitro metabolic stability and permeability combined with in vivo oral bioavailability, panel CYP inhibitor co-administration via different routes, and double cannulation rats were conducted to elucidate the intestinal and hepatic first-pass effect of YL-IPA08 on bioavailability. Unbound brain-to-plasma ratio (Kp,uu) in rats was determined at steady state. Results indicated that P450-mediated elimination appeared to be important for its extensive first-pass effect with comparative contribution of gut (35%) and liver (17%), and no significant species difference was observed. The unbound concentration of YL-IPA08 in rat brain (6.5 pg/ml) was estimated based on Kp,uu (0.18) and was slightly higher than in vitro TSPO-binding activity (4.9 pg/ml). Based on the onset efficacy of YL-IPA08 toward TPSO in brain and Kp,uu, therapeutic human plasma concentration was predicted to be ∼27.2 ng/ml would easily be reached even with unfavorable bioavailability.


BioFactors ◽  
2016 ◽  
Vol 42 (5) ◽  
pp. 533-544 ◽  
Author(s):  
Xiaoting Tian ◽  
Yu Gao ◽  
Zhou Xu ◽  
Shan Lian ◽  
Yuanjie Ma ◽  
...  
Keyword(s):  

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.


1994 ◽  
Vol 71 (01) ◽  
pp. 147-153 ◽  
Author(s):  
Siw Frebelius ◽  
Ulf Hedin ◽  
Jesper Swedenborg

SummaryThe thrombogenicity of the vessel wall after endothelial denudation is partly explained by an impaired inhibition of thrombin on the subendothelium. We have previously reported that thrombin coagulant activity can be detected on the vessel wall after balloon injury in vivo. The glycosaminoglycans of the subendothelium differ from those of the endothelium and have a lower catalyzing effect on antithrombin III, but inhibition of thrombin can still be augmented by addition of antithrombin III to the injured vessel surface.In this study the effect of antithrombin III and heparin on thrombin coagulant activity on the vessel wall was studied after in vivo balloon injury of the rabbit aorta using biochemical and immunohistochemical methods and thrombin was analysed after excision of the vessel. Continuous treatment with heparin, lasting until sacrifice of the animal, or treatment with antithrombin III resulted in significant reduction of thrombin coagulant activity on the injured aorta. Heparin given only in conjunction with the injury did not prevent thrombin coagulant activity or deposition of fibrin on the surface.The capacity of the injured vessel wall to inhibit thrombin in vitro was improved on aortic segments obtained from animals receiving antithrombin III but not from those given heparin. It is concluded that treatment with antithrombin III interferes with thrombin appearance on the vessel wall after injury and thereby reduces the risk for thrombosis.


2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 324-330
Author(s):  
John B Fortune ◽  
Serena Murphy ◽  
Kimberley Tiller

ABSTRACT Introduction With blunt and penetrating trauma to the chest, warfighters and civilians frequently suffer from punctured lung (pneumothorax) and/or bleeding into the pleural space (hemothorax). Optimal management of this condition requires the rapid placement of a chest tube to evacuate as much of the blood and air as possible. Incomplete drainage of blood leading to retained hemothorax may be the result of the final tube tip position not being in contact with the blood collections. To address this problem, we sought to develop a “steerable” chest tube that could be accurately placed or repositioned into a specific desired position in the pleural space to assure optimal drainage. An integrated infusion cannula was added for the instillation of anticoagulants to maintain tube patency, thrombolytics for clot lysis, and analgesics for pain control if required. Materials and Methods A triple-lumen tube was designed to provide a channel for a pull-wire which was wound around an axle integrated into a small proximal handle and controlled by a ratcheted thumbwheel. Tension on the wire creates an arc on the tube that allows for positioning. In vitro testing focused on the relationship between the tension on the pull-wire and the resultant arc. Two adult cadavers and two anesthetized pigs were used to study the feasibility of accurate tube placement. After a brief training session, providers were asked to place tubes inferiorly along the diaphragm where blood was anticipated to accumulate or at the apex of the lung for pneumothorax. Success was determined with fluoroscopic images and was judged as a tube tip lying in the targeted position. Results The design was prototyped with an extruded polyvinyl chloride multilumen tube and a 3D printed tensioning handle. In vitro studies showed that one turn of the thumbwheel created 70° to 90° of arc of the tube. Cadaver and animal studies showed consistent success in the desired placement of the tube at or near the lateral diaphragm or in the apex. Attempts were also successful by surgical residents with minimal training. Conclusions Initial preliminary studies on a novel steerable chest tube have demonstrated the ability to appropriately position the tube in a desired location. The addition of an extendable cannula will allow for safe clot lysis or maintained tube patency. Additional studies are planned to confirm the benefit of this device in preventing retained hemothorax.


2021 ◽  
pp. 159101992110191
Author(s):  
Muhammad Waqas ◽  
Weizhe Li ◽  
Tatsat R Patel ◽  
Felix Chin ◽  
Vincent M Tutino ◽  
...  

Background The value of clot imaging in patients with emergent large vessel occlusion (ELVO) treated with thrombectomy is unknown. Methods We performed retrospective analysis of clot imaging (clot density, perviousness, length, diameter, distance to the internal carotid artery (ICA) terminus and angle of interaction (AOI) between clot and the aspiration catheter) of consecutive cases of middle cerebral artery (MCA) occlusion and its association with first pass effect (FPE, TICI 2c-3 after a first attempt). Results Patients ( n = 90 total) with FPE had shorter clot length (9.9 ± 4.5 mm vs. 11.7 ± 4.6 mm, P = 0.07), shorter distance from ICA terminus (11.0 ± 7.1 mm vs. 14.7 ± 9.8 mm, P = 0.048), higher perviousness (39.39 ± 29.5 vs 25.43 ± 17.6, P = 0.006) and larger AOI (153.6 ± 17.6 vs 140.3 ± 23.5, P = 0.004) compared to no-FPE patients. In multivariate analysis, distance from ICA terminus to clot ≤13.5 mm (odds ratio (OR) 11.05, 95% confidence interval (CI) 2.65–46.15, P = 0.001), clot length ≤9.9 mm (OR 7.34; 95% CI 1.8–29.96, P = 0.005), perviousness ≥ 19.9 (OR 2.54, 95% CI 0.84–7.6, P = 0.09) and AOI ≥ 137°^ (OR 6.8, 95% CI 1.55–29.8, P = 0.011) were independent predictors of FPE. The optimal cut off derived using Youden’s index was 6.5. The area under the curve of a score predictive of FPE success was 0.816 (0.728–0.904, P < 0.001). In a validation cohort ( n = 30), sensitivity, specificity, positive and negative predictive value of a score of 6–10 were 72.7%, 73.6%, 61.5% and 82.3%. Conclusions Clot imaging predicts the likelihood of achieving FPE in patients with MCA ELVO treated with the aspiration-first approach.


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