Platelet Damage Accumulation and Recovery due to Hemodynamic Shear Stresses: An In Vitro Study

2008 ◽  
Author(s):  
Jawaad Sheriff ◽  
Jolyon Jesty ◽  
Danny Bluestein
Keyword(s):  
Shear Stress ◽  
Damage Accumulation ◽  
Heart Valves ◽  
In Vitro Study ◽  
Shear Stresses ◽  
Special Importance ◽  
Prosthetic Devices ◽  
Recovery Potential ◽  
Low Shear

It is well established that shear stress exposure activates platelets, and it has been shown that this flow-induced activation contributes significantly to thromboembolic complications in mechanical heart valves (MHVs) [1]. In addition, the platelet activation state (PAS) assay has been demonstrated to be an efficient technique to measure procoagulant activity [2]. However, there is a lack of reliable models to predict platelet damage accumulation. Such a tool allows thrombogenicity optimization of implanted prosthetic devices. Prior to developing this tool, certain aspects of platelet behavior in response to shear stress must be elucidated. Of special importance for developing accountable damage accumulation models is the recovery potential of platelets during repeated passages through devices, when not exposed to the elevated stresses characterizing blood flow in these devices. To accomplish this, PAS measurements were conducted in a Hemodynamic Shearing Device (HSD), where platelets were exposed to prescribed waveforms with alternating periods of high and low shear stresses.

Velocity and Shear Stress Distribution Downstream of Mechanical Heart Valves in Pulsatile Flow

1989 ◽  
Vol 12 (4) ◽  
pp. 261-269 ◽  
Author(s):  
M. Giersiepen ◽  
U. Krause ◽  
E. Knott ◽  
H. Reul ◽  
G. Rau
Keyword(s):  
Shear Stress ◽  
Heart Valves ◽  
Laser Doppler Anemometry ◽  
Fluid Dynamic ◽  
In Vitro Study ◽  
Turbulent Shear ◽  
Momentum Exchange ◽  
Jude Medical ◽  
Turbulent Shear Stress

Ten mechanical valves (TAD 27 mm): Starr-Edwards Silastic Ball, Björk-Shiley Standard, Björk-Shiley Concave-Convex, Björk-Shiley Monostrut, Hall-Kaster (Medtronic-Hall), OmniCarbon, Bicer Val, Sorin, Saint-Jude Medical and Hemex (Duromedics) are investigated in a comparative in vitro study. The velocity and turbulent shear stress profiles of the valves were determined by Laser Doppler anemometry in two different downstream axes within a model aortic root. Depending on the individual valve design, velocity peaks up to 1.5 m/s and turbulent shear stress peaks up to 150 N/m2 were measured during the systolic phase. These shear stress peaks mainly occurred in areas of flow separation and intense momentum exchange. Directly downstream of the valves (measuring axis 0.55.dAorta) turbulent shear stress peaks occurred at peak systole and during the deceleration phase, while in the second measuring axis (1.5.dAorta) turbulence levels were lower. Shear stress levels were high at the borders of the fluid jets. The results are discussed from a fluid-dynamic point of view.

In Vitro Study of Pulsatile Flow Through a Motionless Diode Valve in the Pulmonary Position

2009 ◽  
Author(s):  
Tiffany A. Camp ◽  
Richard Figliola ◽  
Donald Beasley ◽  
Timothy Conover ◽  
Tim McQuinn ◽  
...  
Keyword(s):  
Shear Stress ◽  
In Vitro Study ◽  
Mechanical Valve ◽  
Field Analysis ◽  
Shear Stresses ◽  
Flow Shear ◽  
Flow Through ◽  
Flow Field Analysis ◽  
Stress Patterns

Pulmonary circulation shows a tolerance for mild regurgitation and pressure gradient. [1]. Given these tolerances, we have explored using a fluid diode as a pulmonary valve. Camp et al showed that diode valves are able to regulate flow in the pulmonary position with promising results and could be tolerated using a pig model [2, 3]. Flow and shear stress patterns are two other hemodynamic concerns that must be considered during heart valve design. Elevated bulk flow shear stresses, wall shear stresses, and turbulent stresses within bioprostheses and mechanical valve flow fields are recognized as a cause of cell and platelet damage, initiating platelet activation and triggers for thrombogenesis [4–7]. In this study, we conduct in vitro flow field analysis of the flow downstream of a proposed prototype diode valve in order to observe the flow and shear stress patterns.

scholarly journals Computational Analysis of Fluid Flow Within a Device for Applying Biaxial Strain to Cultured Cells

2015 ◽  
Vol 137 (5) ◽  
Author(s):  
Jason Lee ◽  
Aaron B. Baker
Keyword(s):  
Shear Stress ◽  
Cultured Cells ◽  
Fluid Velocity ◽  
Mechanical Strain ◽  
Cell Types ◽  
Linear Increase ◽  
Shear Stresses ◽  
Biaxial Strain ◽  
Maximal Strain

In vitro systems for applying mechanical strain to cultured cells are commonly used to investigate cellular mechanotransduction pathways in a variety of cell types. These systems often apply mechanical forces to a flexible membrane on which cells are cultured. A consequence of the motion of the membrane in these systems is the generation of flow and the unintended application of shear stress to the cells. We recently described a flexible system for applying mechanical strain to cultured cells, which uses a linear motor to drive a piston array to create biaxial strain within multiwell culture plates. To better understand the fluidic stresses generated by this system and other systems of this type, we created a computational fluid dynamics model to simulate the flow during the mechanical loading cycle. Alterations in the frequency or maximal strain magnitude led to a linear increase in the average fluid velocity within the well and a nonlinear increase in the shear stress at the culture surface over the ranges tested (0.5–2.0 Hz and 1–10% maximal strain). For all cases, the applied shear stresses were relatively low and on the order of millipascal with a dynamic waveform having a primary and secondary peak in the shear stress over a single mechanical strain cycle. These findings should be considered when interpreting experimental results using these devices, particularly in the case when the cell type used is sensitive to low magnitude, oscillatory shear stresses.

Hemodynamic Shear Stress And Endothelial Cell Function: In Vitro Studies

1981 ◽  
Author(s):  
M A Gimbrone ◽  
C F Dewey ◽  
P F Davies ◽  
S R Bussolari
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Fluid Shear Stress ◽  
Cell Structure ◽  
Structure And Function ◽  
Cellular Migration ◽  
Shear Stresses ◽  
Endothelial Cell Function ◽  
And Function

The vascular endothelial lining in vivo is constantly subjected to hemodynamic shear stresses resulting from normal and altered patterns of blood flow. To facilitate the study of effects of fluid shear stress on endothelial cell structure and function, we have developed an in vitro system, utilizing a cone-plate apparatus, to subject coverslip cultures of bovine aortic endothelial cells (BAEC) to controlled levels of shear (up to 102 dynes/cm2) in either laminar or turbulent flow. The magnitude and direction of shear stress within the system are accurately known from both theory and experimental measurements. The data reported here are for laminar flow. Subconfluent BAEC cultures continuously exposed to 1-5 dynes/cm2 shear proliferated at a rate comparable to that of static cultures, and postconfluent monolayers appeared unaltered morphologically for up to 1 week. In contrast, BAEC cultures (both postconfluent and subconfluent) exposed to 8 dynes/cm2 developed dramatic, time-dependent morphological changes. By 48 hrs, cells uniformly assumed an ellipsoidal configuration, with their major axes aligned in the direction of flow. Exposure to >10 dynes/cm2 caused variable cell detachment from plain glass substrates. Cellular migration into linear “wounds”, created in confluent areas, was influenced by both the direction and amplitude of applied shear. Exposure to 8 dynes/ cm2 induced functional alterations, including increased fluid (bulk phase) endocytosis, prostaglandin production and platelet reactivity. These observations indicate that fluid mechanical forces can directly influence endothelial cell structure and function. Hemodynamic modulation of endothelial cell behavior may be relevant to normal vessel wall physiology, as well as the pathogenesis of atherosclerosis and thrombosis.

Eulerian-Eulerian Multiphase Modeling of Blood Cells Segregation in Flow Through Microtubes

2017 ◽  
Author(s):  
Yertay Mendygarin ◽  
Luis R. Rojas-Solórzano ◽  
Nurassyl Kussaiyn ◽  
Rakhim Supiyev ◽  
Mansur Zhussupbekov
Keyword(s):  
Shear Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Heart Diseases ◽  
Accurate Determination ◽  
Shear Stresses ◽  
High Shear ◽  
Blood Damage ◽  
Solid Phases

Cardiovascular Diseases, the common name for various Heart Diseases, are responsible for nearly 17.3 million deaths annually and remain the leading global cause of death in the world. It is estimated that this number will grow to more than 23.6 million by 2030, with almost 80% of all cases taking place in low and middle income countries. Surgical treatment of these diseases involves the use of blood-wetted devices, whose relatively recent development has given rise to numerous possibilities for design improvements. However, blood can be damaged when flowing through these devices due to the lack of biocompatibility of surrounding walls, thermal and osmotic effects and most prominently, due to the excessive exposure of blood cells to shear stress for prolonged periods of time. This extended exposure may lead to a rupture of membrane of red blood cells, resulting in a release of hemoglobin into the blood plasma, in a process called hemolysis. Moreover, exposure of platelets to high shear stresses can increase the likelihood of thrombosis. Therefore, regions of high shear stress and residence time of blood cells must be considered thoroughly during the design of blood-contacting devices. Though laboratory tests are vital for design improvements, in-vitro experiments have proven to be costly, time-intensive and ethically controversial. On the other hand, simulating blood behavior using Computational Fluid Dynamics (CFD) is considered to be an inexpensive and promising tool to help predicting blood damage in complex flows. Nevertheless, current state-of-the-art CFD models of blood flow to predict hemolysis are still far from being fully reliable and accurate for design purposes. Previous work have demonstrated that prediction of hemolysis can be dramatically improved when using a multiphase (i.e., phases are plasma, red blood cells and platelets) model of the blood instead of assuming the blood as a homogeneous mixture. Nonetheless, the accurate determination of how the cells segregate becomes the critical issue in reaching a truthful prediction of blood damage. Therefore, the attempt of this study is to develop and validate a numerical model based on Granular Kinetic Theory (GKT) for solid phases (i.e., cells treated as particles) that provides an improved prediction of blood cells segregation within the flow in a microtube. Simulations were based on finite volume method using Eulerian-Eulerian modeling for treatment of three-phase (liquid-red blood cells and platelets) flow including the GKT to deal with viscous properties of the solid phases. GKT proved to be a good model to predict particle concentration and pressure drop by taking into account the contribution of collisional, kinetic and frictional effects in the stress tensor of the segregated solid phases. Preliminary results show that the improved segregated model leads to a better prediction of spatial distribution of blood cells. Simulations were performed using ANSYS FLUENT platform.

Identification of a Mathematical Model for the Prediction of Platelet Damage Accumulation in Artificial Organs: A Preliminary Study

2007 ◽  
Author(s):  
Matteo Nobili ◽  
Jawaad Sheriff ◽  
Umberto Morbiducci ◽  
Alberto Redaelli ◽  
Danny Bluestein
Keyword(s):  
Platelet Activation ◽  
Damage Accumulation ◽  
Heart Valves ◽  
Implantable Devices ◽  
Artificial Organs ◽  
Model Parameters ◽  
Reliable Technique ◽  
Prosthetic Devices ◽  
High Incidence ◽  
Preliminary Study

Platelets are the pre-eminent cell involved in hemostasis and thrombosis. In recent years it has been demonstrated that flow-induced platelet activation is a major cause for the relatively high incidence of thromboembolic complications in mechanical heart valves (MHVs) [1,2].The platelet activation state (PAS) assay has proved to be a reliable technique for the experimental measurement of procoagulant activity [3]. A Predictive numerical model for platelets damage accumulation could provide critical information for thrombogenicity optimization of implantable prosthetic devices. This would lead to improving the safety and efficacy of implantable devices. Reliable models able to predict this phenomenon are still lacking. The aim of this work is an attempt to bridge this gap. A model for describing the activation of formed elements in blood requires establishing a correlation between mechanical loading, exposure time and the phenomenological response of these elements to it. A physically consistent phenomenological model is used [4] and genetic algorithms (GAs) [5], have been successfully applied to the tuning of the model parameters by correlating its predictions to PAS measurements conducted in a Hemodynamic Shearing Device (HSD) by exposing platelets to prescribed shear stress loading waveforms.

Computational Prediction of Fluid Induced Stress States in Dynamically Conditioned Engineered Heart Valve Tissues

2012 ◽  
Author(s):  
M. Salinas ◽  
D. Schmidt ◽  
R. Lange ◽  
M. Libera ◽  
S. Ramaswamy
Keyword(s):  
Shear Stress ◽  
Steady Flow ◽  
Heart Valve ◽  
Heart Valves ◽  
Critical Role ◽  
Computational Prediction ◽  
Mechanical Conditioning ◽  
Custom Made ◽  
Stress Environments

There is extensive documented evidence that mechanical conditioning plays a significant role in the development of tissue grown in-vitro for heart valve scaffolds [1–3]. Modern custom made bioreactors have been used to study the mechanobiology of engineered heart valve tissues [1]. Specifically fluid-induced shears stress patterns may play a critical role in up-regulating extracellular matrix secretion by progenitor cell sources such as bone marrow derived stem cells (BMSCs) [2] and increasing the possibility of cell differentiation towards a heart valve phenotype. We hypothesize that specific biomimetic fluid induced shear stress environments, particularly oscillatory shear stress (OSS), have significant effects on BMSCs phenotype and formation rates. As a first step here, we attempt to quantify and delineate the entire 3-D flow field by developing a CFD model to predict the fluid induced shear stress environments on engineered heart valves tissue under quasi-static steady flow and dynamic steady flow conditions.

Evaluation Of Platelet Reactivity In Patients With Abnormal Heart Valves

1981 ◽  
Author(s):  
J M Riddle ◽  
D J Magllligan ◽  
P D Stein
Keyword(s):  
Aortic Stenosis ◽  
Mitral Stenosis ◽  
Heart Valves ◽  
Platelet Reactivity ◽  
Normal Subjects ◽  
Bioprosthetic Valve ◽  
Shear Stresses ◽  
Mean Values ◽  
Transmission Electron

The reactivity of platelets from 57 patients was evaluated prior to removal of either an abnormal natural mitral or aortic valve or a degenerated porcine bioprosthetic valve. Thirty patients had aortic stenosis or insufficiency, 21 had mitral stenosis or insufficiency, and 6 underwent the removal of a long-term (4 to 7 years after insertion) Hancock porcine bioprosthetic valve. Transmission electron microscopy was used in a standardized in vitro method to evaluate these platelets. The degree of surface activation (cytoplasmic spreading by single platelets) and aggregate formation were both recorded. A hyperactive response was defined as >20% of the spread type platelet and/or an increased number of aggregates (>93 aggregates/100 single platelets). Hyperactive platelet populations were found in only 8% (6 of 72) of normal subjects. In contrast, 60% (18 of 30) of patients with aortic stenosis or insufficiency, 76%, (16 of 21) of patients with mitral stenosis or insufficiency, and 83%, (5 of 6) of patients with a degenerated porcine valve showed hyperactive platelets. The mean percentage of the spread type platelet for the various groups was 40, 38 and 30 respectively with corresponding mean values of 106, 124 and 102 for platelet aggregates. The reactivity of platelets from the normal group differed significantly from each group of patients with abnormal valves (P > 0.01). However, the level of platelet reactivity between the patient groups with abnormal valves did not differ significantly. Disturbed flow, high shear stresses and the exposure of potentially thrombotic materials are all features associated with abnormal natural heart valves as well as a degenerated bioprosthesis and may explain our finding of increased platelet reactivity in these patients.

Flow-induced dilation of rat soleus feed arteries

1997 ◽  
Vol 273 (5) ◽  
pp. H2423-H2427 ◽  
Author(s):  
Jeffrey L. Jasperse ◽  
M. Harold Laughlin
Keyword(s):  
Shear Stress ◽  
Maximum Flow ◽  
Intraluminal Pressure ◽  
Shear Stresses ◽  
Potential Contribution ◽  
Basal Diameter ◽  
Exercise Hyperemia ◽  
Feed Arteries

Flow-induced dilation is thought to contribute to dilation of skeletal muscle arteries and arterioles during exercise hyperemia. We sought to determine whether rat soleus feed arteries (SFA) exhibit flow-induced dilation and to evaluate the potential contribution of flow-induced dilation of SFA to exercise hyperemia. Rat SFA were isolated and cannulated to allow pressure and intraluminal flow to be independently controlled. Intraluminal pressure was maintained at 90 cmH2O throughout the experiment. All SFA ( n = 13) developed spontaneous tone and dilated in response to flow. Flow of 10 and 14 μl/min produced a 34 ± 14 and 56 ± 17 μm increase above basal diameter (135 ± 12 μm), respectively. Flows >14 μl/min produced little further dilation. Maximum flow-induced dilation was 86 ± 3% of passive diameter determined in calcium-free physiological saline solution. Calculated shear stress was maintained at 4–6 dyn/cm2 at flows of 10–20 μl/min but increased at greater flows because SFA did not dilate further. To determine whether dilation in response to flows in this range may contribute to exercise hyperemia, we estimated in vivo SFA blood flows from previously published soleus blood flow data. Anesthetized rats are estimated to have flows of 10 μl/min per SFA, and conscious rats are estimated to have flows of 95 (nonexercising), 153 (walking), and 225 (running) μl/min per SFA. Corresponding shear stresses were estimated to be 26 (anesthetized), 47 (conscious, nonexercising), 75 (walking), and 111 (running) dyn/cm2. Because estimated in vivo values for both flow and wall shear stress are far greater than the flow and/or shear stresses at which maximal flow-induced dilation occurs in vitro, we conclude that flow-induced dilation contributes little to dilation of SFA during locomotory exercise.

scholarly journals P2834An in vitro study on the influence of increased heart rate on the right ventricular kinetic energy and shear stresses

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
U Gulan ◽  
A M Saguner ◽  
D Akdis ◽  
A Denegri ◽  
M X Miranda ◽  
...  
Keyword(s):  
Heart Rate ◽  
Kinetic Energy ◽  
Right Ventricular ◽  
In Vitro Study ◽  
Vitro Study ◽  
Shear Stresses ◽  
The Right
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