Role of high shear rate in thrombosis

Casa, Lauren D. C.; Deaton, David N.; Ku, David N.

doi:10.1016/j.jvs.2014.12.050

Cited by 220 publications

(204 citation statements)

References 52 publications

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“…The exact mechanism of mtDNA release in this setting was not investigated. Turbulent flow may have resulted in activation of clotting cascades or lysis of cells [36, 37]. Similarly, endotracheal tube placement in surgery has been associated with higher concentrations of mtDNA in throat lavage fluid.…”

Section: Release Of Cf-mtdna Via Cell Necrosis In Trauma and Surgerymentioning

confidence: 99%

The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies

Thurairajah

Briggs

Balogh

2018

Eur J Trauma Emerg Surg

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Mitochondria play a key role in the pathophysiology of post-injury inflammation. Cell-free mitochondrial DNA (cf-mtDNA) is now understood to catalyse sterile inflammation after trauma. Observations in trauma cohorts have identified high cf-mtDNA in patients with systemic inflammatory response syndrome and multiple organ failure as well as following major surgery. The source of cf-mtDNA can be various cells affected by mechanical and hypoxic injury (passive mechanism) or induced by inflammatory mechanisms (active mechanism). Multiple forms of cf-mtDNA exist; mtDNA fragments, mtDNA in microparticles/vesicles and cell-free mitochondria. Trauma to cells that are rich in mitochondria are believed to release more cf-mtDNA. This review describes the current understanding of the mechanisms of cf-mtDNA release, its systemic effects and the potential therapeutic implications related to its modification. Although current understanding is insufficient to change trauma management, focussed research goals have been identified to pave the way for monitoring and manipulation of cf-mtDNA release and effects in trauma.

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Section: Release Of Cf-mtdna Via Cell Necrosis In Trauma and Surgerymentioning

confidence: 99%

The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies

Thurairajah

Briggs

Balogh

2018

Eur J Trauma Emerg Surg

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“…Shear rates higher than 5000 s −1 are considered as pathological and shear rates higher than 8000-10 000 s −1 activate von Willebrand Factor. 14,21 Therefore, all shear rates above 10 000 s −1 are considered as relevant. The CTA scale computational model showed an elevated shear rate downstream of the stenosis, which was a result of inertial forces in the curved section after the stenosis.…”

Section: Computational Fluid Dynamics On the 3d Vessel Geometriesmentioning

confidence: 99%

“…It has been shown that shear rate is very important in von Willebrand factor activation and thus influences platelet adhesion and aggregation. 14,15,20,21 However, due to inherent limitations posed by 2D wafer-based microfabrication techniques of microfluidic chips, the channels in almost all onchip thrombosis models inevitably possess planar configurations with rectangular cross-sections instead of the typical 3D, round cross-section blood vessel structures found in vivo. 11,22 A number of strategies have been employed to produce chips that contain microfluidic channels with circular cross-sections.…”

Section: Introductionmentioning

confidence: 99%

Mimicking arterial thrombosis in a 3D-printed microfluidic in vitro vascular model based on computed tomography angiography data

et al. 2017

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Arterial thrombosis is the main instigating factor of heart attacks and strokes, which result in over 14 million deaths worldwide every year. The mechanism of thrombosis involves factors from the blood and the vessel wall, and it also relies strongly on 3D vessel geometry and local blood flow patterns. Microfluidic chipbased vascular models allow controlled in vitro studies of the interaction between vessel wall and blood in thrombosis, but until now, they could not fully recapitulate the 3D geometry and blood flow patterns of real-life healthy or diseased arteries. Here we present a method for fabricating microfluidic chips containing miniaturized vascular structures that closely mimic architectures found in both healthy and stenotic blood vessels. By applying stereolithography (SLA) 3D printing of computed tomography angiography (CTA) data, 3D vessel constructs were produced with diameters of 400 μm, and resolution as low as 25 μm. The 3D-printed templates in turn were used as moulds for polydimethylsiloxane (PDMS)-based soft lithography to create microfluidic chips containing miniaturized replicates of in vivo vessel geometries. By applying computational fluid dynamics (CFD) modeling a correlation in terms of flow fields and local wall shear rate was found between the original and miniaturized artery. The walls of the microfluidic chips were coated with human umbilical vein endothelial cells (HUVECs) which formed a confluent monolayer as confirmed by confocal fluorescence microscopy. The endothelialised microfluidic devices, with healthy and stenotic geometries, were perfused with human whole blood with fluorescently labeled platelets at physiologically relevant shear rates. After 15 minutes of perfusion the healthy geometries showed no sign of thrombosis, while the stenotic geometries did induce thrombosis at and downstream of the stenotic area. Overall, the novel methodology reported here, overcomes important design limitations found in typical 2Dwafer-based soft lithography microfabrication techniques and shows great potential for controlled studies of the role of 3D vessel geometries and blood flow patterns in arterial thrombosis.

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“…More importantly, discrepancies may be attrib- 16 Moreover, high shear rates cause explosive platelet thrombosis associated with life-threatening hemorrhage or arterial occlusion. 17 Even though attempts have been made to improve the hemodynamic characteristics of coronary artery bypasses, 18 the performance of the resulting configurations remains controversial.…”

Section: Study Limitationsmentioning

confidence: 99%

Analysis of Computational Fluid Dynamics and Particle Image Velocimetry Models of Distal-End Side-to-Side and End-to-Side Anastomoses for Coronary Artery Bypass Grafting in a Pulsatile Flow

Shintani

Iino

Yamamoto

et al. 2018

Circ J

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deSTS anastomosis has not yet been reported. This study is designed to investigate flow fields in deSTS-simulated left internal thoracic artery (LITA)-left anterior descending artery (LAD) anastomoses, examine differences between deSTS and ETS anastomoses in flow fields using computational fluid dynamics (CFD), and validate the findings via particle image velocimetry (PIV). MethodsThe internal thoracic artery (ITA) is a proven excellent conduit to use when performing CABG. ETS or deSTS anastomoses are usually used to connect the distal end of the ITA-LAD anastomoses. Therefore, in our model, it was assumed that the anastomoses were to the distal end of the LITA-LAD anastomoses.A series of separate studies were performed. First, steady and pulsatile flows were investigated in an actual size model (Model A) using CFD. Next, CFD simulations and PIV measurements of the steady flow were used to validate C oronary artery bypass grafting (CABG) has long been used to facilitate arterial revascularization. Anastomotic intimal hyperplasia (IH) is a major cause of graft failure. It has been shown that hemodynamic factors are involved in IH formation and progression. 1,2 These factors include disturbed blood flow patterns, low and oscillating wall shear stress (WSS), sufficiently high WSS, large spatial WSS gradients, and the stagnation of blood cells. 3, 4 Grafts to the coronary artery commonly involve end-toside (ETS) anastomoses. It has been shown that, after such procedures, IH develops predominantly at the toe and heel of such anastomoses and on the arterial floor across the junction, where the disturbance of flow patterns and other hemodynamic factors have reportedly been observed. 2, 5 Meanwhile, several recent studies have reported the usefulness of distal-end side-to-side (deSTS) anastomoses. 6,7 Umezu et al 8 reported that deSTS anastomoses lose less energy than ETS anastomoses. However, a detailed 3-dimensional assessment of the hemodynamic characteristics of Background: Intimal hyperplasia (IH) is a major cause of graft failure. Hemodynamic factors such as stagnation and disturbed blood flow are involved in IH formation. The aim of this study is to perform a comparative analysis of distal-end side-to-side (deSTS) and endto-side (ETS) anastomoses using computational fluid dynamics (CFD) after validating the results via particle image velocimetry (PIV).

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Role of high shear rate in thrombosis

Cited by 220 publications

References 52 publications

The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies

The source of cell-free mitochondrial DNA in trauma and potential therapeutic strategies

Mimicking arterial thrombosis in a 3D-printed microfluidic in vitro vascular model based on computed tomography angiography data

Analysis of Computational Fluid Dynamics and Particle Image Velocimetry Models of Distal-End Side-to-Side and End-to-Side Anastomoses for Coronary Artery Bypass Grafting in a Pulsatile Flow

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