Low Background, Pulsatile, In Vitro Flow Circuit for Modeling Coronary Implant Thrombosis

2002 ◽  
Vol 124 (6) ◽  
pp. 662-668 ◽  
Author(s):  
Kumaran Kolandaivelu ◽  
Elazer R. Edelman
Keyword(s):  
Wall Motion ◽  
Flow Patterns ◽  
Oscillating Flow ◽  
Control Loops ◽  
Occlusion Time ◽  
Flow Generation ◽  
Type Flow ◽  
Pulsatile Flows ◽  
Flow Circuit

We have developed an in vitro method for creating pulsatile flows to mimic coronary type flow patterns on a beat-to-beat basis. The flow is created by accelerating fluid loops about an axis, inducing relative wall motion. Using this technique, a variety of oscillating flow patterns can be generated and modulated. Such flow generation offers the potential to monitor sensitive, flow-dependent, biological parameters like thrombosis while minimizing background disturbances from pump action and circuit effects. We examined this potential by measuring the loop occlusion time for loops stented with stainless steel 7-9 NIR® stents and stentless control loops.

Flow and Particle Dispersion in a Pulmonary Alveolus—Part I: Velocity Measurements and Convective Particle Transport

2010 ◽  
Vol 132 (5) ◽  
Author(s):  
Sudhaker Chhabra ◽  
Ajay K. Prasad
Keyword(s):  
Particle Transport ◽  
Vector Fields ◽  
Wall Motion ◽  
Flow Patterns ◽  
Particle Dispersion ◽  
Alveolar Wall ◽  
Spherical Cap ◽  
Image Velocimetry ◽  
Transport And Mixing

The alveoli are the smallest units of the lung that participate in gas exchange. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region (∼500 μm), the transport and deposition of inhaled aerosol particles are influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step toward predicting aerosol transport and deposition in the human acinar region. In this study, flow patterns and particle transport have been measured using a simplified in-vitro alveolar model consisting of a single alveolus located on a bronchiole. The model comprises a transparent elastic 5/6 spherical cap (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). The alveolus is capable of expanding and contracting in phase with the oscillatory flow through the tube. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns in the alveolus. Data were acquired for five cases obtained as combinations of the alveolar-wall motion (nondeforming/oscillating) and the bronchiole flow (none/steady/oscillating). Detailed vector maps at discrete points within a given cycle revealed flow patterns, and transport and mixing of bronchiole fluid into the alveolar cavity. The time-dependent velocity vector fields were integrated over multiple cycles to estimate particle transport into the alveolar cavity and deposition on the alveolar wall. The key outcome of the study is that alveolar-wall motion enhances mixing between the bronchiole and the alveolar fluid. Particle transport and deposition into the alveolar cavity are maximized when the alveolar wall oscillates in tandem with the bronchiole fluid, which is the operating case in the human lung.

Flow patterns from metallic vascular endoprostheses: in vitro results

2001 ◽  
Vol 11 (5) ◽  
pp. 893-901 ◽  
Author(s):  
S. Müller-Hülsbeck ◽  
J. Grimm ◽  
T. Jahnke ◽  
G. Häselbarth ◽  
M. Heller
Keyword(s):  
Flow Patterns

scholarly journals Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 659
Author(s):  
Konstantinos Stamatopoulos ◽  
Sharad Karandikar ◽  
Mark Goldstein ◽  
Connor O’Farrell ◽  
Luca Marciani ◽  
...  
Keyword(s):  
Particle Motion ◽  
Wall Motion ◽  
Bulk Liquid ◽  
Cine Mri ◽  
Fluid Viscosity ◽  
Positron Emission ◽  
Volume Viscosity ◽  
Viscosity Fluid

This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon.

scholarly journals Migfilin supports hemostasis and thrombosis through regulating platelet αIIbβ3 outside-in signaling.

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2608-2618
Author(s):  
Yangfan Zhou ◽  
Mengjiao Hu ◽  
Xiaoyan Chen ◽  
Shuai Wang ◽  
Jingke Li ◽  
...  
Keyword(s):  
Signaling Molecules ◽  
Dense Granule ◽  
Regulation Mechanism ◽  
Filamin A ◽  
Characteristic Functional ◽  
Integrin Αiibβ3 ◽  
Occlusion Time ◽  
Dense Granule Secretion

Elucidating the regulation mechanism of integrin αIIbβ3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role of migfilin in the support of platelet αIIbβ3 activation, however, contribution of migfilin to thrombosis and hemostasis in vivo and a detailed mechanism of migfilin in platelets are not known. In this study, with migfilin deletion (migfilin-/-) mice, we report that migfilin is a pivotal positive regulator of hemostasis and thrombosis. Migfilin-/- mice showed a nearly doubled tail-bleeding time and a prolonged occlusion time in Fecl3-induced mesenteric arteriolar thrombosis. Migfilin deficiency impedes platelet thrombi formation on collagen surface and impairs platelet aggregation and dense-granule secretion. Supported by characteristic functional readings and phosphorylation status of distinctive signaling molecules in the bidirectional signaling processes of αIIbβ3, the functional defects of migfilin-/- platelets appear to be mechanistically associated with a compromised outside-in signaling, rather than inside-out signaling. A synthesized cell-permeable migfilin peptide harboring filamin A binding sequence rescued the defective function and phosphorylation of signaling molecules of migfilin-/- platelets. Finally, migfilin does not influence the binding of filamin A and β3 subunit of αIIbβ3 in resting platelets, but hampers the re-association of filamin A and β3 during the conduct of outside-in signaling, suggesting that migfilin functions through regulating the interaction dynamics of αIIbβ3 and filamin A in platelets. Our study enhances the current understanding of platelet integrin αIIbβ3-mediated outside-in signaling and proves that migfilin is an important regulator for platelet activation, hemostasis and thrombosis.

scholarly journals 3D Encapsulation Made Easy: A Coaxial-Flow Circuit for the Fabrication of Hydrogel Microfibers Patches

2019 ◽  
Vol 6 (2) ◽  
pp. 30 ◽  
Author(s):  
Chiara Campiglio ◽  
Francesca Ceriani ◽  
Lorenza Draghi
Keyword(s):  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Closed Loop ◽  
Fiber Diameter ◽  
Cross Linking ◽  
Scaffold Fabrication ◽  
Cell Culturing ◽  
Viable Cells ◽  
Flow Circuit

To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro.

PIV and LIF Measurements in Aortic Dissection Models

2017 ◽  
Author(s):  
Elie Salameh ◽  
Wadih Khoury ◽  
Charbel Saade ◽  
Ghanem F. Oweis
Keyword(s):  
Aortic Dissection ◽  
Flow Behavior ◽  
False Lumen ◽  
Blood Stream ◽  
Flow Patterns ◽  
Vascular Abnormalities ◽  
Transport Dynamics ◽  
Mixing Behavior ◽  
Contrast Ct

In this work an in-vitro flow experiment is conducted to elucidate the flow behavior in simplified aortic dissection (AD) disease geometries. In AD, the innermost layer of the aortic wall is locally and partially torn allowing blood to flow between the wall layers forming a parallel blood stream in what is known as the false lumen. The aim of this work is to elucidate the disease flow physics, and to provide guidance in diagnostic radiology, particularly contrast injected computed tomography (CT), where understanding flow patterns and mixing behavior is important for accurate diagnosis. In contrast-CT, dye is injected in the peripheral blood stream to illuminate the blood vessels and identify vascular abnormalities. The flow patterns and the dye transport dynamics impact the nature of the CT images and their interpretation. Particle image velocimetry (PIV) is used to quantify the AD flow fields, and laser-induced fluorescence (LIF) is implemented to visualize and assess the mixing behavior of dye in the false and true lumens. Interesting flow patterns are revealed and discussed in the context of their possible contribution to tear expansion and flapping, and to the elevated mean pressure in the false lumen that is reported in the literature.

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis

2019 ◽  
Vol 39 (04) ◽  
pp. 392-397
Author(s):  
Wei Wang ◽  
Songqing Lai ◽  
ZiJin Xiao ◽  
Haiyue Yan ◽  
Yongxi Li ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiplatelet Agent ◽  
Wnt Signalling ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Platelet Activity ◽  
Occlusion Time ◽  
Negative Effect

AbstractPlatelets play a crucial role in haemostasis and several pathophysiological processes. Collagen is a main initiator for platelet activation and aggregation. Given that Wnt signalling negatively regulates platelet function, and IWR-1 (a small molecule inhibitor for Wnt signalling) has the potential of inhibiting collagen synthesis, it is essential to investigate whether IWR-1 regulates collagen-induced platelet activation and protects against thrombogenesis. In the present study we found that IWR-1 pretreatment effectively suppressed collagen-induced platelet aggregation in a dose-dependent manner. In addition, IWR-1 also resulted in a decrease of P-selectin and phosphatidylserine surface exposure using fluorescence-activated cell sorting analysis. In vitro studies further revealed that IWR-1 had a negative effect on integrin a2β1 activation and platelet spreading. More importantly, the results from in vivo studies showed that IWR-1 exhibited a robust bleeding diathesis in the tail-bleeding assay and a prolonged occlusion time in the FeCl3-induced carotid injury model. Taken together, current results demonstrate that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new antiplatelet agent.

Phenotypic Correction of Adamts13-Deficient Mice by Early Intra-Amniotic Gene Transfer of Lentiviral Vector Encoding ADAMTS13 Genes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 197-197
Author(s):  
Masami Niiya ◽  
Masayuki Endo ◽  
Philip W. Zoltick ◽  
Nidal E. Muvarak ◽  
David G. Motto ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Proteolytic Activity ◽  
Lentiviral Vector ◽  
Wild Type ◽  
Occlusion Time ◽  
Carboxyl Terminal ◽  
Human Wild Type

Abstract ADAMTS13, a member of A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS) family, is mainly synthesized in the hepatic stellate cells, endothelial cells and megakaryocytes or platelets. It controls the sizes of von Willebrand factor (VWF) multimers by cleaving VWF at the Tyr1605-Met1606 bond. Genetic deficiency of plasma ADAMTS13 activity results in hereditary thrombotic thrombocytopenic purpura (TTP), also named Upshaw-Schülman syndrome. To develop a potential gene therapy approach and to determine the domains of ADAMTS13 required for recognition and cleavage of VWF in vivo, a self-inactivating lentiviral vector encoding human wild-type ADAMTS13 or variant truncated after the spacer domain (construct MDTCS) was administrated by intra-amniotic injection on embryonic day 8. Direct stereomicroscopy and immunofluorescent microscopic analysis revealed that the green fluorescent protein (GFP) reporter, ADAMTS13 and MDTCS were predominantly expressed in the heart, kidneys and skin. The synthesized ADAMTS13 and truncated variant were detectable in mouse plasma by immunoprecipitation and Western blot, as well as by proteolytic cleavage of FRETS-VWF73 substrate. The levels of proteolytic activity in plasma of mice expressing ADAMTS13 and MDTCS were 5 ± 7% and 60 ± 70%, respectively using normal human plasma as a standard, and this proteolytic activity persisted for at least 24 weeks in Adamts13−/−mice and 42 weeks in wild-type mice tested (the duration of observation). The mice expressing both recombinant ADAMTS13 and MDTCS showed a significantly decreased ratio of plasma VWF collagen-binding activity to antigen and a reduction in VWF multimer sizes as compared to those in the controls. Moreover, the mice expressing ADAMTS13 and MDTCS showed a significant prolongation of ferric chloride-induced carotid arterial occlusion time (9.0 ± 0.6 and 25.2 ± 3.2 min, respectively) as compared to the Adamts13−/− mice expressing GFP alone (5.6 ± 0.5 min) (p<0.01). The ferric chloride-induced carotid occlusion time in Adamts13−/− mice expressing ADAMTS13 was almost identical to that in wild type mice with same genetic background (C56BL/6) (8.0 ± 0.2 min) (p>0.05). The data demonstrate the correction of the prothrombotic phenotype in Adamts13−/−mice by gene transfer to the fetus by viral vectors encoding human wild type ADAMTS13 and the carboxyl terminal truncated variant (MDTCS), supporting the feasibility of developing a gene therapy based treatment for hereditary TTP. The discrepancy in the proteolytic activity of MDTCS between in vitro (Zhang P et al. Blood, 2007 in press) and in vivo in the present study suggests the potential cofactors in murine circulation that may rescue the defective proteolytic activity of the carboxyl-terminal truncated ADAMTS13 protease seen in vitro.

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