scholarly journals Pharmacological Blockade of Glycoprotein VI Promotes Thrombus Disaggregation in the Absence of Thrombin

2020 ◽  
Vol 40 (9) ◽  
pp. 2127-2142 ◽  
Author(s):  
Muhammad Usman Ahmed ◽  
Valeria Kaneva ◽  
Stéphane Loyau ◽  
Dmitry Nechipurenko ◽  
Nicolas Receveur ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Atherosclerotic Plaque ◽  
Numerical Models ◽  
Recombinant Tissue Plasminogen Activator ◽  
Arterial Blood Flow ◽  
Glycoprotein Vi ◽  
Signalling Molecules ◽  
Arterial Blood ◽  
Platelet Disaggregation ◽  
Platelet Aggregates

Objective: Atherothrombosis occurs upon rupture of an atherosclerotic plaque and leads to the formation of a mural thrombus. Computational fluid dynamics and numerical models indicated that the mechanical stress applied to a thrombus increases dramatically as a thrombus grows, and that strong inter-platelet interactions are essential to maintain its stability. We investigated whether GPVI (glycoprotein VI)-mediated platelet activation helps to maintain thrombus stability by using real-time video-microscopy. Approach and Results: We showed that GPVI blockade with 2 distinct Fab fragments promoted efficient disaggregation of human thrombi preformed on collagen or on human atherosclerotic plaque material in the absence of thrombin. ACT017-induced disaggregation was achieved under arterial blood flow conditions, and its effect increased with wall shear rate. GPVI regulated platelet activation within a growing thrombus as evidenced by the loss in thrombus contraction when GPVI was blocked, and the absence of the disaggregating effect of an anti-GPVI agent when the thrombi were fully activated with soluble agonists. The GPVI-dependent thrombus stabilizing effect was further supported by the fact that inhibition of any of the 4 key immunoreceptor tyrosine-based motif signalling molecules, src-kinases, Syk, PI3Kβ, or phospholipase C, resulted in kinetics of thrombus disaggregation similar to ACT017. The absence of ACT017-induced disaggregation of thrombi from 2 afibrinogenemic patients suggests that the role of GPVI requires interaction with fibrinogen. Finally, platelet disaggregation of fibrin-rich thrombi was also promoted by ACT017 in combination with r-tPA (recombinant tissue plasminogen activator). Conclusions: This work identifies an unrecognized role for GPVI in maintaining thrombus stability and suggests that targeting GPVI could dissolve platelet aggregates with a poor fibrin content.

scholarly journals Wave Propagation in Thin-Walled Aortic Analogues

2008 ◽  
Author(s):  
C. G. Giannopapa ◽  
J. M. B. Kroot
Keyword(s):  
Experimental Data ◽  
Wave Propagation ◽  
Frequency Domain ◽  
Analytical Model ◽  
Viscoelastic Properties ◽  
Numerical Models ◽  
Computational Cost ◽  
Arterial Blood Flow ◽  
One Dimensional ◽  
Arterial Blood

Research wave propagation in liquid filled vessels is often motivated by the need to understand arterial blood flow. Theoretical and experimental investigation of the propagation of waves in flexible tubes has been studied by many researchers. The analytical one dimensional frequency domain wave theory has a great advantage of providing accurate results without the additional computational cost related to the modern time domain simulation models. For assessing the validity of analytical and numerical models well defined in-vitro experiments are of great importance. The objective of this paper is to present a frequency domain transmission line analytical model based on one-dimensional wave propagation theory and validate it against experimental data obtained for aortic analogues. The elastic and viscoelastic properties of the wall are included in the analytical model. The pressure, flow and wall distention results obtained from the analytical model are compared with experimental data in two straight tubes with aortic relevance. The analytical models and the experimental measurements were found to be in good agreement when the viscoelastic properties of the wall are taken into account.

Multiple Reflection and Transmission Theory for Wave Propagation in the Aorta

2009 ◽  
Author(s):  
C. G. Giannopapa ◽  
J. M. B. Kroot
Keyword(s):  
Experimental Data ◽  
Wave Propagation ◽  
Frequency Domain ◽  
Analytical Model ◽  
Numerical Models ◽  
Computational Cost ◽  
Arterial Blood Flow ◽  
Transition Line ◽  
One Dimensional ◽  
Arterial Blood

Wave propagation in liquid filled vessels is often motivated by the need to understand arterial blood flow. Theoretical and experimental investigations of traveling waves in flexible tubes have been performed by many researchers. The analytical one dimensional frequency domain wave theory has a great advantage of providing accurate results without the additional computational cost involved in the modern time domain simulation models. Transition line theory allows including non uniformities of vessels by capturing them as several uniform segments. For assessing the validity of analytical and numerical models well defined in-vitro experiments are of great importance. The objective of this paper is to present a frequency domain transmission line analytical model based on one-dimensional wave propagation theory and validate it against experimental data obtained for aortic analogues. The analytical model is set up by multiple sections and a formulation is derived that incorporates the multiple reflections and transmissions of propagating waves through the interfaces of these sections. The aortic analogues include straight and tapered tubes. The pressure, flow and wall distention results obtained from the analytical model are compared with experimental data in two straight tubes and one tapered one with aortic relevance. The analytical models and the experimental measurements were found to be in good agreement for both the uniform and tapered tubes.

Multiple Reflection Theory for Fluid-Structure Interaction in Viscoelastic Vessels and Experimental Validation

2016 ◽  
Author(s):  
J. M. B. Kroot ◽  
C. G. Giannopapa
Keyword(s):  
Experimental Data ◽  
Numerical Models ◽  
Fluid Structure Interaction ◽  
Analytical Theory ◽  
Arterial Blood Flow ◽  
Transition Line ◽  
Multiple Reflections ◽  
Fluid Structure ◽  
Structure Interaction ◽  
Arterial Blood

Fluid-structure interaction in viscoelastic vessels is often modelled with the motivation to understand arterial blood flow. Traveling waves in flexible vessels have been analyzed and experiments have been performed by many researchers. Theoretical models often focus either on the flow of the liquid (assuming that the wall is rigid), or on the displacement of the wall (assuming that the wall is elastic). Analytical theories on the interaction between the fluid and the wall are limited; models are typically based on numerical techniques. For assessing the validity of analytical and numerical models well-defined in-vitro experiments are of great importance. The objective of this paper is to present a transmission line analytical theory and validate it against experimental data obtained for aortic analogues. Transition line theory allows for including non-uniformities of vessels by capturing them as several uniform segments. The analytical theory is set up by multiple sections and a formulation is derived that incorporates the multiple reflections and transmissions of propagating waves through the interfaces of these sections. The pressure, flow and wall distention results obtained from the analytical model are compared with experimental data from a straight uniform tube and a tapered one with aortic relevance. The analytical results and the experimental measurements were found to be in good agreement for both the uniform and tapered tubes.

Liver bud transplantation in rats

2018 ◽  
Vol 71 (4) ◽  
pp. 163-169
Author(s):  
Eiji Kobayashi ◽  
Shin Enosawa
Keyword(s):  
Fetal Liver ◽  
Liver Parenchyma ◽  
Arterial Blood Flow ◽  
Silk Suture ◽  
Cell Sheets ◽  
Human Liver Tissue ◽  
Arterial Blood ◽  
Matrix Cell ◽  
Experimental Microsurgery

Abstract: Introduction: Research has made progress in organ fabrication using an extracellular matrix, cell sheets, or organoids. Human liver tissue has been constructed using a 3-dimensional (3D) bioprinter and showed evidence that an in vitro generated liver bud was reformed in a rodent liver model. This study describes the stages of development of rat fetal organs and liver structure and reviews recent progress in liver organoid transplantation. Methods: The authors developed the procedures for creating a transected plane for use in experimental microsurgery in rats. A liver lobe was fixed vertically with gauze and it was ligated with 6-0 silk suture in the cut line; the parenchyma was cut, and major vessels were ligated to create the transected plane. The ligated tissue was carefully resected. Hemostasis was not required and hepatic components remained on the transected plane. The plane was covered by omentum. Results: Using this model, we transplanted fetal liver or a 3D bioprinted liver organoid. This microsurgical method enabled creation of an intact liver parenchyma plane. No bleeding was observed. The transplanted liver components successfully engrafted on the liver. Conclusion: This method may provide an essential environment for growing liver using portal and arterial blood flow.

Modeling Elastic Walls in Lattice Boltzmann Simulations of Arterial Blood Flow

2013 ◽  
Vol 23 (2) ◽  
Author(s):  
Xenia Descovich ◽  
Giuseppe Pontrelli ◽  
Sauro Succi ◽  
Simone Melchionna ◽  
Manfred Bammer
Keyword(s):  
Blood Flow ◽  
Lattice Boltzmann ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Lattice Boltzmann Simulations ◽  
Elastic Walls

scholarly journals Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 353
Author(s):  
Jayasree Nair ◽  
Lauren Davidson ◽  
Sylvia Gugino ◽  
Carmon Koenigsknecht ◽  
Justin Helman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Perinatal Asphyxia ◽  
Arterial Blood Flow ◽  
Positive Pressure ◽  
Optimal Timing ◽  
Delayed Cord Clamping ◽  
Arterial Blood ◽  
Cord Clamping ◽  
Sustained Inflation ◽  
Near Term

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.

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