Trackability of distal access catheters: an in vitro quantitative evaluation of navigation strategies.

BACKGROUND: In mechanical thrombectomy (MT), distal access catheters (DACs) are tracked through the vascular anatomy to reach the occlusion site. The inability of DACs to reach the occlusion site has been reported as a predictor of unsuccessful recanalization. This study aims to provide insight into how to navigate devices through the vascular anatomy with minimal track forces, since higher forces may imply more risk of vascular injuries. METHODS: We designed an experimental setup to monitor DAC track forces when navigating through an in vitro anatomical model. Experiments were recorded to study mechanical behaviors such as tension buildup against vessel walls, DAC buckling, and abrupt advancements. A multiple regression analysis was performed to predict track forces from the catheters' design specifications. RESULTS: DACs were successfully delivered to the target M1 in 60 of 63 in vitro experiments (95.2%). Compared to navigation with unsupported DAC, the concomitant coaxial use of a microcatheter/microguidewire and microcatheter/stent retriever anchoring significantly reduced the track forces by about 63% and 77%, respectively (p<0.01). The presence of the braid pattern in the reinforcement significantly reduced the track forces regardless of the technique used (p<0.05). Combined coil and braid reinforcement configuration, as compared with coil alone, and a thinner distal wall were predictors of lower track force when navigating with unsupported DAC. CONCLUSIONS: The use of microcatheter and stent retriever facilitate smooth navigation of DACs through the vascular tortuosity to reach the occlusion site, which in turn improves the reliability of tracking when positioning the DAC closer to the thrombus interface.

Numerical modeling of bare and polymer-covered braided stents using torsional and tensile springs connectors.

Computational modeling of braided stents using the finite element (FE) method has become an essential tool in the design and development of these medical devices. One of the most challenging issues in such a task is representing in an accurate manner the interaction between the interlacing wires. With the goal of achieving a compromise between accuracy and computational affordability, we propose a new approach consisting in using 1D FE formulations equipped with torsional springs at the crossover points of the wires. In the case of covered braided stents, the model is enriched with a set of tensile springs (defined in the longitudinal direction), aimed at capturing the stiffening effect of the polymeric membrane. The predictive capabilities of the proposed model are evaluated using data of our own experimental tests, as well as data from other tests in the literature. The simulations demonstrate that the proposed model is able to predict the (markedly nonlinear) behavior of stents when subjected to radial and axial cycle loads, with errors at the end of the compression stage ranging from 0.5% to 10% in all cases.

Suction force rather than aspiration flow correlates with recanalization in hard clots: an in vitro study model.

BACKGROUND: ANA Advanced Neurovascular Access provides a novel funnel component designed to reduce clot fragmentation and facilitate retrieval in combination with stent-retrievers (SRs) in stroke patients by restricting flow and limiting clot shaving. In previous publications ANA presented excellent in vitro/in vivo efficacy data, especially with fibrin-rich hard clots. We aimed to determine the main physical property responsible for these results, namely suction force versus aspiration flow. METHODS: We evaluated in a bench model the suction force and flow generated by ANA and compared them to other neurovascular catheters combined with a SR (Solitaire). Aspiration flow was evaluated with a flow rate sensor while applying vacuum pressure with a pump. Suction force was determined using a tensile strength testing machine and a purposely designed tool that completely seals the device tip simulating complete occlusion by a hard clot. Suction force was defined as the force needed to separate the device from the clot under aspiration. All experiments were repeated five times, and mean values used for comparisons. RESULTS: Aspiration flow increased with the inner diameter of the device: ANA 1.85±0.04 mL/s, ACE68 3.74±0.05 mL/s, and 8F-Flowgate2 5.96±0.30 mL/s (P<0.001). After introducing the SR, the flow was reduced by an average of 0.57±0.12 mL/s. Due to its larger distal surface, ANA suction force (1.69±0.40 N) was significantly higher than ACE68 (0.26±0.04 N) and 8F-Flowgate2 (0.42±0.06 N) (P<0.001). After introducing the SR, suction force variation was not relevant except for ANA that increased to 2.64±0.41 N. CONCLUSION: Despite lower in vitro aspiration flow, the ANA design showed a substantially higher suction force than other thrombectomy devices.

A captured room temperature stable Wheland intermediate as a key structure for the orthogonal decoration of 4-amino-pyrido[2,3-d]pyrimidin-7(8H)-ones.

Wheland intermediates are usually unstable compounds and only a few have been isolated at very low temperatures. During our work on tyrosine kinase inhibitors, we studied the bromination of 7 in order to obtain a dibromo substituted pyrido[2,3-d]pyrimidin-7(8H)-one which could be orthogonally decorated. Surprisingly, treatment of 7 with 3 equiv. of Br2 in acetic acid (AcOH) afforded 12, a captured room temperature stable Wheland bromination intermediate stabilized by the bromination of the imino tautomer of the amino group at C4 of the pyridopyrimidine skeleton. The structure was confirmed by crystal structure determination from powder X-ray diffraction data. Treatment of 12 with DMSO afforded the dibromo substituted compound 13 presenting a bromine atom at C6 and C5-C6 unsaturation. 13 was directly accessed by treating 7 with N-bromosuccinimide (NBS), a protocol extended to other compounds using NBS or N-iodosuccinimide (NIS) to afford 6-halo substituted systems. 26, bearing an iodine at C6 and a p-bromophenylamino at C2, allows the orthogonal decoration of pyridopyrimidines.

Preclinical evaluation of the ANCD thrombectomy device: safety and efficacy in a swine clot model.

BACKGROUND: The Advanced Thrombectomy System (ANCD) provides a new funnel component designed to reduce clot fragmentation and facilitate retrieval in patients with stroke by locally restricting flow, allowing distal aspiration in combination with a stent retriever (SR). OBJECTIVE: To evaluate the preclinical efficacy and safety of the ANCD in a swine clot model. METHODS: Soft and firm clots were implanted in the lingual and cervical arteries of 11 swine to obtain Thrombolysis in Cerebral Infarction (TICI) 0 blood flow. Mechanical thrombectomy was performed with either a balloon guide catheter+Solitaire 2 stent retriever (BGC+SR, n=13) or ANCD+SR (n=13). TICI flow was evaluated and successful revascularization was defined as TICI 3 (normal perfusion). To characterize safety, a total of 3 passes were performed in each vessel independent of recanalization. Tissues were explanted for histopathological analysis after 3 and 30 days, respectively. RESULTS: First pass reperfusion rates were ANCD+SR: 69% and BGC+SR: 46%. Reperfusion increased after the third pass in both groups (ANCD+SR: 100%, vs BGC+SR: 77%). Recanalization was achieved after an average of 1.4 and 1.9 passes in ANCD+SR and BGC+SR (p=0.095), respectively. Vessel injury was comparable in both groups; endothelial loss at 3 days was the most common injury seen (ANCD+SR: 1.78±1.22; BGC+SR: 2.03±1.20; p=0.73), while other histopathological markers were absent or minimal. Tissues downstream from targeted vessels also showed absence or minimal lesions across both groups. CONCLUSIONS: Results in a swine clot model support the high efficacy of the ANCD+SR without causing clinically significant vessel injury potentially related to the new funnel component.

ANCD thrombectomy device: in vitro evaluation.

INTRODUCTION: Endovascular treatment of stroke, although highly effective, may fail to reach complete recanalization in around 20% of cases. The Advanced Thrombectomy System (ANCD) is a novel stroke thrombectomy device designed to reduce clot fragmentation and facilitate retrieval by inducing local flow arrest and allowing distal aspiration in combination with a stent retriever. We aimed to assess the preclinical efficacy of ANCD. METHODS: Soft red blood cell (RBC)-rich (n=20/group) and sticky fibrin-rich (n=30/group) clots were used to create middle cerebral artery (MCA) occlusions in two vascular phantoms. Three different treatment strategies were tested: (1) balloon guide catheter + Solitaire (BGC+SR); (2) distal access catheter + SR (DAC+SR); and (3) ANCD+SR, until complete recanalization was achieved or to a maximum of three passes. The recanalization rate was determined after each pass. RESULTS: After one pass, ANCD+SR resulted in an increased recanalization rate (94%) for all clots together compared with BGC+SR (66%; p<0.01) or DAC+SR (80%; p=0.04). After the final pass the recanalization rate increased in all three groups but remained higher with ANCD+SR (100%) than with BGC+SR (74%; p<0.01) or DAC+SR (90%; p=0.02). The mean number of passes was lower with ANCD+SR (1.06) than with BGC+SR (1.46) or DAC+SR (1.25) (p=0.01). A logistic regression model adjusted for treatment arm, clot type, and model used showed that both RBC-rich clots (OR 8.1, 95% CI 1.6 to 13.5) and ANCD+SR (OR 3.9, 95% CI 1.01 to 15.8) were independent predictors of first-pass recanalization. CONCLUSION: In in vitro three-dimensional models replicating MCA-M1 occlusion, ANCD+SR showed significantly better recanalization rates in fewer passes than other commonly used combinations of devices.

Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,ß-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,ß-unsaturated ester, malononitrile, and an aryl substituted guanidine.