scholarly journals Thrombectomy aspiration device geometry optimization for removal of blood clots in cerebral vessels

2020 ◽  
Vol 14 (1) ◽  
pp. 6229-6237
Author(s):  
C. Talayero ◽  
G. Romero ◽  
G. Pearce ◽  
J. Wong
Keyword(s):  
Robust Design ◽  
Blood Clot ◽  
Cerebral Vessels ◽  
Environment Change ◽  
Aspiration Thrombectomy ◽  
Catheter Design ◽  
Blood Clots ◽  
Potential Damage

A study involving the removal of blood clots in cerebral vessels by aspiration thrombectomy is presented. A robust design for the distal end geometry of a catheter is obtained that, together with adequate suction conditions, could avoid potential damage in the artery or fragmentation the thrombus. The optimization process of the parameters is undertaken by a Design of Experiments (DOE) that has been prepared based on Robust Design theories. In particular, 27 experiments are run for one factor at 9 levels (catheter geometry) and up to 9 factors at 3 levels. The experiments are formulated with virtual models that are solved with computing tools. Co-simulation between Computer Fluid Dynamics (CFD) and Finite Elements Method (FEM) structural analysis was used to obtain the suction conditions and the behavior of the blood clot during the intervention process. By comparing the results of the 27 experiments, the highest values of the suctioning force are obtained for a hole pattern based catheter design, that also gives the lowest risk for clot damage (based on the stress value obtained). Direct aspiration and designs based on conical catheter distal ends, give less robust solutions (results are not stable when the conditions of the environment change). Our study investigated the distance between the catheter and the clot, and it was noted that if the catheter was far from the clot, the suction generated a vessel narrowing and consequent potential damage. Up to 90 kPa could be applied when suctioning at a maximum distance equal to the diameter of the vessel between the distal end of the catheter and the proximal end of the clot. A maximum suctioning force of 0,514N was achieved without damage to the artery or the clot. This research enables us to determine and use the most representative parameters and geometries to be tested in in-vitro and in-vivo experiments. In this virtual study, hypothesizes are assumed with regard to the material properties, but the robustness of the design process allows to expect similar results in future in-vitro and in-vivo tests.

scholarly journals Modeling of blood clot removal with aspiration Thrombectomy devices

2020 ◽  
Vol 14 (1) ◽  
pp. 6238-6250
Author(s):  
G. Romero ◽  
C. Talayero ◽  
G. Pearce ◽  
J. Wong
Keyword(s):  
Mathematical Model ◽  
Interventional Procedure ◽  
Fluid Dynamic ◽  
Blood Clot ◽  
Bond Graph ◽  
Graph Models ◽  
Aspiration Thrombectomy ◽  
Potential Damage ◽  
Mass Spring

Thrombectomy by aspiration is a highly effective method of accomplishing vessel recanalization. This study aims to obtain a mathematical model that allows the prediction of the dynamic response of a thrombus in response to different suction conditions, in order to avoid potential damage or the breakage of the clot during the interventional procedure. Virtual computing models have been created using Bond-Graph data and mass-spring Multi-Degree of Freedom equations. The model allows the use of tensile and torsion loads that could potentially be generated by the suction pressure together with different catheter geometries. The stress generated in the clot depends on its length and on its stiffness. The results obtained with the mathematical model are validated with a Finite Element Method (FEM) model, shows good agreement in terms of stress and elongation values. The results are consistent with previous Bond Graph models which indicated that the forces needed to extract a blood clot from an artery in in-vitro experiments are within the range used experimentally (~40-90 kPa). Qualitative experiments are undertaken with 3D printed scale prototypes and gelatin. The results are consistent with Computer Fluid Dynamic (CFD) simulations.

Hemostatic wound dressings: Predicting their effects by in vitro tests

2019 ◽  
Vol 33 (9) ◽  
pp. 1285-1297 ◽  
Author(s):  
Cornelia Wiegand ◽  
Martin Abel ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Michael Zieger ◽  
...  
Keyword(s):  
Blood Clot ◽  
Wound Dressings ◽  
In Vitro Tests ◽  
Regenerated Cellulose ◽  
Oxidized Regenerated Cellulose ◽  
Inflammatory Reactions ◽  
In Vitro Techniques ◽  
Cotton Gauze

Background Application of controlled in vitro techniques can be used as a screening tool for the development of new hemostatic agents allowing quantitative assessment of overall hemostatic potential. Materials and methods Several tests were selected to evaluate the efficacy of cotton gauze, collagen, and oxidized regenerated cellulose for enhancing blood clotting, coagulation, and platelet activation. Results Visual inspection of dressings after blood contact proved the formation of blood clots. Scanning electron microscopy demonstrated the adsorption of blood cells and plasma proteins. Significantly enhanced blood clot formation was observed for collagen together with β-thromboglobulin increase and platelet count reduction. Oxidized regenerated cellulose demonstrated slower clotting rates not yielding any thrombin generation; yet, led to significantly increased thrombin-anti-thrombin-III complex levels compared to the other dressings. As hemostyptica ought to function without triggering any adverse events, induction of hemolysis, instigation of inflammatory reactions, and initiation of the innate complement system were also tested. Here, cotton gauze provoked high PMN elastase and elevated SC5b-9 concentrations. Conclusions A range of tests for desired and undesired effects of materials need to be combined to gain some degree of predictability of the in vivo situation. Collagen-based dressings demonstrated the highest hemostyptic properties with lowest adverse reactions whereas gauze did not induce high coagulation activation but rather activated leukocytes and complement.

scholarly journals Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1207
Author(s):  
Andrea Vítečková Wünschová ◽  
Adam Novobilský ◽  
Jana Hložková ◽  
Peter Scheer ◽  
Hana Petroková ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Imaging Techniques ◽  
Barium Sulphate ◽  
Flow Conditions ◽  
Preclinical Imaging ◽  
Blood Clots ◽  
3D Printed

Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.

scholarly journals TITANIUM NANOPARTICLES CONJUGATED WITH STREPTOKINASE AS A MODIFIED THROMBOLYTIC AGENT

2020 ◽  
pp. 18-25
Author(s):  
HAYDER H. ABED ◽  
ESTABRAQ AR. ALWASITI ◽  
AMIR T. TAWFEEQ
Keyword(s):  
Thrombolytic Agent ◽  
Blood Clot ◽  
Control Group ◽  
Thrombolytic Activity ◽  
Protein Assay ◽  
Blood Clots ◽  
Ft Ir ◽  
Titanium Nanoparticles ◽  
D Dimer

Objective: Blood clots are the main cause of death worldwide by stroke and myocardial infarction. Streptokinase a thrombolytic agent that is used in the treatment of circulatory disorders. Methods: Titanium Nanoparticles was supplied from Changsha Santech Co. Its characterized were studied using (FT-IR, XRD, AFM, FE-SEM). Streptokinase at concentration 0.1 mg/ml was conjugated with Titanium nanoparticles using PH equal to 5.2 with continuous stirring. Formation of Streptokinase loading Titanium nanoparticles confirmed using FT-IR, Ninhydrine’s test and Bradford protein assay. Physicochemical Properties were studied in vitro. Thrombolytic activity in vitro was determined using d–dimer indicator and weight of blood clot after treatment as indicators of thrombolytic activity. Results: Titanium nanoparticles show particle size at range 31 nm. The thrombolytic activity of streptokinase loading Titanium nanoparticles shows significant value in d-dimer and weight of blood clot compared with the control group and non-significant compared with an equivalent amount of streptokinase alone. Conclusion: Titanium nanoparticles conjugated with streptokinase show high thrombolytic activity against blood clots in vitro.

Effect of Progesterone and Synthetic Progestins on Whole Blood Clot Formation and Erythrocyte Structure

2017 ◽  
Vol 23 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Albe C. Swanepoel ◽  
Odette Emmerson ◽  
Etheresia Pretorius
Keyword(s):  
Whole Blood ◽  
Blood Clot ◽  
Thrombotic Event ◽  
Clot Formation ◽  
Erythrocyte Aggregation ◽  
Erythrocyte Morphology ◽  
Increased Risk ◽  
Blood Clots ◽  
Membrane Ultrastructure

AbstractCombined oral contraceptive (COC) use is a risk factor for venous thrombosis (VT) and related to the specific type of progestin used. VT is accompanied by inflammation and pathophysiological clot formation, that includes aberrant erythrocytes and fibrin(ogen) interactions. In this paper, we aim to determine the influence of progesterone and different synthetic progestins found in COCs on the viscoelasticity of whole blood clots, as well as erythrocyte morphology and membrane ultrastructure, in an in vitro laboratory study. Thromboelastography (TEG), light microscopy, and scanning electron microscopy were our chosen methods. Our results point out that progestins influence the rate of whole blood clot formation. Alterations to erythrocyte morphology and membrane ultrastructure suggest the presence of eryptosis. We also note increased rouleaux formation, erythrocyte aggregation, and spontaneous fibrin formation in whole blood which may explain the increased risk of VT associated with COC use. Although not all COC users will experience a thrombotic event, individuals with a thrombotic predisposition, due to inflammatory or hematological illness, should be closely monitored to prevent pathological thrombosis.

scholarly journals In vitro experiments of cerebral blood flow during aspiration thrombectomy: potential effects on cerebral perfusion pressure and collateral flow

2015 ◽  
Vol 8 (9) ◽  
pp. 969-972 ◽  
Author(s):  
Frank Lally ◽  
Mitra Soorani ◽  
Timothy Woo ◽  
Sanjeev Nayak ◽  
Changez Jadun ◽  
...  
Keyword(s):  
Direct Contact ◽  
Flow Direction ◽  
Flow Characteristics ◽  
Collateral Flow ◽  
In Vitro Experiments ◽  
Aspiration Thrombectomy ◽  
Flow Solver ◽  
Catheter Tip

BackgroundMechanical thrombectomy with stent retriever devices is associated with significantly better outcomes than thrombolysis alone in the treatment of acute ischemic stroke. Thrombus aspiration achieves high patency rates, but clinical outcomes are variable. The aim of this study was to examine the effect of different suction conditions on perfusate flow during aspiration thrombectomy.MethodsA computational fluid dynamics model of an aspiration device within a patent and occluded blood vessel was used to simulate flow characteristics using fluid flow solver software. A physical particulate flow model of a patent vessel and a vessel occluded by thrombus was then used to visualize flow direction and measure flow rates with the aspiration catheter placed 1–10 mm proximal of the thrombus, and recorded on video.ResultsThe mathematical model predicted that, in a patent vessel, perfusate is drawn from upstream of the catheter tip while, in an occluded system, perfusate is drawn from the vessel proximal to the device tip with no traction on the occlusion distal of the tip. The in vitro experiments confirmed the predictions of this model. In the occluded vessel aspiration had no effect on the thrombus unless the tip of the catheter was in direct contact with the thrombus.ConclusionsThese experiments suggest that aspiration is only effective if the catheter tip is in direct contact with the thrombus. If the catheter tip is not in contact with the thrombus, aspirate is drawn from the vessels proximal of the occlusion. This could affect collateral flow in vivo.

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 743-754 ◽  
Author(s):  
Robert A. S. Ariëns ◽  
Thung-Shenq Lai ◽  
John W. Weisel ◽  
Charles S. Greenberg ◽  
Peter J. Grant
Keyword(s):  
Genetic Polymorphisms ◽  
Factor Xiii ◽  
Blood Clot ◽  
Site Directed Mutagenesis ◽  
Clot Formation ◽  
Factor Xiiia ◽  
Clotting Factors ◽  
Functional Features

Abstract Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease.

scholarly journals Oxidation of Bilirubin Produces Compounds that Cause Prolonged Vasospasm of Rat Cerebral Vessels: A Contributor to Subarachnoid Hemorrhage–Induced Vasospasm

2002 ◽  
Vol 22 (4) ◽  
pp. 472-478 ◽  
Author(s):  
Joseph F. Clark ◽  
Melinda Reilly ◽  
Frank R. Sharp
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Stress Protein ◽  
Cerebral Vessels ◽  
Oxidation Products ◽  
Adult Rats ◽  
Cranial Window ◽  
Related Stress ◽  
Protein Response

The authors have previously shown that bilirubin-oxidation products (BOXes) are present in CSF of subarachnoid hemorrhage patients with vasospasm, and that BOXes cause vasoconstriction in vitro. This study determined whether BOXes cause vasospasm in vivo. Identical volumes of either lysed blood or standardized amounts of BOXes were injected into the cisterna magna of adult rats. BOX injections caused 6 of 10 rats to die within 10 minutes, whereas 12 of 12 rats survived for 24 hours after blood injections. The mechanism for this significant ( P ⩽ 0.01) increase in mortality was unclear. To directly test whether BOXes produced vasospasm, a cranial window technique was used. Application of 20 μL of 10-μmol/L bilirubin had little effect on the vessels. However, application of BOXes produced marked, dose-dependent small artery and arteriole vasospasm that approached a 90% decrease in diameter by 40 minutes after application in some vessels, and persisted for at least 24 hours. To determine if BOX-mediated vasospasm led to cortical injury, histology and immunocytochemistry were performed on animals that survived for 24 hours. There was a BOX-related stress protein response for HSP25 and HSP32 (HO-1) without evidence of infarction. The finding that the BOXes produce vasospasm of cerebral vessels in vivo, in conjunction with BOXes being found in CSF of vasospasm patients, supports our hypothesis that BOXes contribute to or cause cerebral vasospasm after subarachnoid hemorrhage.

scholarly journals The alternatively spliced V region contributes to the differential incorporation of plasma and cellular fibronectins into fibrin clots.

1992 ◽  
Vol 119 (4) ◽  
pp. 923-933 ◽  
Author(s):  
C L Wilson ◽  
J E Schwarzbauer
Keyword(s):  
Blood Clot ◽  
Coagulation Factor ◽  
Factor Xiiia ◽  
Cross Linking ◽  
Asymmetric Distribution ◽  
Alternatively Spliced ◽  
V Region ◽  
Fibrin Clots

During blood clot formation in vivo, plasma fibronectin (pFN) is cross-linked to fibrin by coagulation factor XIIIa. Cellular FN (cFN), which localizes to connective tissue, is distinguished from pFN by the inclusion of alternatively spliced segments. To determine if these two FNs are functionally equivalent in blood clotting, the cross-linking of rat pFN and cFN to fibrin was compared in an in vitro clotting assay. Fibrinogen and FN were incubated at physiological ratios in the presence of thrombin and factor XIIIa. Cross-linking of FN to fibrin was monitored by SDS-PAGE and immunoblotting. Over 24 h, cFN was incorporated at a significantly slower rate than pFN and was not completely cross-linked to fibrin at a temperature that favors this interaction (0 degrees C). This difference was observed with purified fibrinogens from human, rat, and bovine and with rat plasma and was maintained even after incubation of pFN with rat fibroblasts for several days. Using the same assay, purified recombinant V(+)-V0 and V(+)-V+ FN dimers resembling pFN and cFN, respectively, showed a similar difference in cross-linking kinetics. These results suggest that the asymmetric distribution of the V region among pFN dimers plays a role in regulating its incorporation into blood clots. In fibrin clots, cFN was converted into a set of cross-linked intermediates distinct from those of pFN. For example, while pFN was initially cross-linked into a pFN-fibrin alpha heterodimer, this product was not a major intermediate in clots formed with cFN. This finding, in conjunction with evidence for the formation of factor XIIIa-catalyzed cFN-cFN cross-links, indicated that cFN molecules interact with each other, and with fibrin, differently from pFN. Together, these results show an important functional distinction between pFN and cFN.

scholarly journals A preliminary investigation of in vitro anti-thrombotic and anti-platelet activity of Pinus Gerardiana

2017 ◽  
Vol 4 (1) ◽  
pp. 1098 ◽  
Author(s):  
Atta-ur Rehman ◽  
Sara Naz ◽  
Muhammad Zaman ◽  
Syed Saeed-ul-Hassan ◽  
Javed Iqbal ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Blood Clot ◽  
Preliminary Investigation ◽  
Circulatory System ◽  
Clot Lysis ◽  
Platelet Activity ◽  
In Vivo Models ◽  
The Stability

Introduction: Hemostasis is a process which preserves the stability of a closed and high-pressure circulatory system after any vascular injury. Circulating platelets are recruited to the site of injury, where they develop a major component of the developing thrombus, blood clotting, started by tissue factor, concludes in the generation of thrombin and fibrin. Thrombosis is a serious event in the arterial diseases and a major cause in the development of myocardial infarction, stroke and venous thrombo-embolism which justify prominent morbidity and mortality rate. The knowledge of molecular and cellular mechanism of the formation of thrombus has developed considerably in the recent studies by using different in-vitro and in-vivo models of diseases. P. gerardiana nut oil has been reported to possess anti-bacterial, anti-fungal, anti-viral, anti-septic, anti-neuralgic, diuretic, expectorant, hypertensive properties. However, hardly, any data is available regarding effects of nut oil on platelet function. In this study, fibrinolytic activity and effect on platelet aggregation were investigated. Method: P. gerardiana nut oil was extracted by using n-Hexane and then concentrated by rotary evaporator. Anti-thrombotic and fibrinolytic activities were evaluated on blood clot formation. Effects on platelet aggregation of the oil were determined based on collagen or epinephrine induced platelet aggregation. Results: P. gerardiana caused blood clot lysis in-vitro. P. gerardiana nut oil inhibited collagen dependent platelet aggregation while accelerated the epinephrine dependent platelet aggregation. In vitro whole blood coagulation was also reduced. In vivo P. gerardiana nut oil has no significant effect on blood cell indices. Conclusion: P. gerardiana nuts oil can be an effective therapy for the treatment of cardiovascular disorders and thromboembolism.

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