Shear Stress Waveforms Research Articles

Fabricating a multi-component microfluidic system for exercise-induced endothelial cell mechanobiology guided by hemodynamic similarity

Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments. First, based on the equivalent of blood pressure (BP) and wall shear stress (WSS) waveforms, we establish a hemodynamic similarity principle to efficiently map the input impedance in vivo to that in vitro, after which the multi-component microfluidic system is designed and fabricated using a lumped parameter hemodynamic model. Second, numerical simulation and experimental studies are carried out to validate the performance of the designed microfluidic system. Finally, the intracellular Ca2+ responses after exposure to different intensities of exercise-induced BP and WSS waveforms are measured to improve the reliability of EC mechanobiological studies using the designed microfluidic system. Overall, the proposed hemodynamic similarity principle can guide the fabrication of a multi-component microfluidic system for endothelial cell mechanobiology.

Parametric Deconvolution for Cancer Cells Viscoelasticity Measurements from Quantitative Phase Images.

In this contribution, we focused on optimising a dynamic flow-based shear stress system to achieve a reliable platform for cell shear modulus (stiffness) and viscosity assessment using quantitative phase imaging. The estimation of cell viscoelastic properties is influenced by distortion of the shear stress waveform, which is caused by the properties of the flow system components (i.e., syringe, flow chamber and tubing). We observed that these components have a significant influence on the measured cell viscoelastic characteristics. To suppress this effect, we applied a correction method utilizing parametric deconvolution of the flow system's optimized impulse response. Achieved results were compared with the direct fitting of the Kelvin-Voigt viscoelastic model and the basic steady-state model. The results showed that our novel parametric deconvolution approach is more robust and provides a more reliable estimation of viscosity with respect to changes in the syringe's compliance compared to Kelvin-Voigt model.

Platelet adhesion potential estimation in a normal and diseased coronary artery model: effects of shear stress magnitude versus shear stress history

Platelets play a salient role in the pathogenesis of coronary diseases; primarily through their adhesion to other platelets, endothelial cells and plasma proteins. It is necessary for platelets to activate in order for them to adhere to these different substrates. One of the key regulatory mechanical factors in platelet activation is shear stress, which has been shown to alter multiple platelet functions through the activation of mechanoreceptors. Our goal was to investigate how different numerical shear stress tracking techniques affect platelet adhesion estimates within physiologically relevant computational models. Previously, we developed a physiological coronary artery computational fluid dynamics model. Shear stress waveforms, obtained from these models, were used to monitor in vitro platelet and endothelial cell adhesion marker expression. In this work, the adhesion marker expression data was regressed to obtain numerical functions for receptor expression predictions. These functions were input into a customized adhesion model utilizing different shear stress tracking techniques. For the normal vascular conditions and minimal pathological disease models, shear stress tracking did not significantly affect the adhesion estimates. However, for the severe pathological model, the two shear stress tracking methods had vastly different estimates. Therefore, shear stress tracking methods must be chosen accurately to predict platelet adhesion potentials for accurate modeling techniques.

A Mechano-Activated Cell Reporter System as a Proxy for Flow-Dependent Endothelial Atheroprotection

The vascular endothelium plays a critical role in the health and disease of the cardiovascular system. Importantly, biomechanical stimuli generated by blood flow and sensed by the endothelium constitute important local inputs that are translated into transcriptional programs and functional endothelial phenotypes. Pulsatile, laminar flow, characteristic of regions in the vasculature that are resistant to atherosclerosis, evokes an atheroprotective endothelial phenotype. This atheroprotective phenotype is integrated by the transcription factor Kruppel-like factor-2 (KLF2), and therefore the expression of KLF2 can be used as a proxy for endothelial atheroprotection. Here, we report the generation and characterization of a cellular KLF2 reporter system, based on green fluorescence protein (GFP) expression driven by the human KLF2 promoter. This reporter is induced selectively by an atheroprotective shear stress waveform in human endothelial cells, is regulated by endogenous signaling events, and is activated by the pharmacological inducer of KLF2, simvastatin, in a dose-dependent manner. This reporter system can now be used to probe KLF2 signaling and for the discovery of a novel chemical-biological space capable of acting as the “pharmacomimetics of atheroprotective flow” on the vascular endothelium.

Routine clinical anti-platelet agents have limited efficacy in modulating hypershear-mediated platelet activation associated with mechanical circulatory support

IntroductionContinuous flow ventricular assist devices (cfVADs) continue to be limited by thrombotic complications associated with disruptive flow patterns and supraphysiologic shear stresses. Patients are prescribed complex antiplatelet therapies, which do not fully prevent recurrent thromboembolic events. This is partially due to limited data on antiplatelet efficacy under cfVAD-associated shear conditions. Materials and methodsWe investigated the efficacy of antiplatelet drugs directly acting on three pathways: (1) cyclooxygenase (aspirin), (2) phosphodiesterase (dipyridamole, pentoxifylline, cilostazol), and (3) glycoprotein IIb-IIIa (eptifibatide). Gel-filtered platelets treated with these drugs were exposed for 10min to either constant shear stresses (30dyne/cm2 and 70dyne/cm2) or dynamic shear stress profiles extracted from simulated platelet trajectories through a cfVAD (Micromed DeBakey). Platelet activation state (PAS) was measured using a modified prothrombinase-based assay, with drug efficacy quantified based on PAS reduction compared to untreated controls. Results and conclusionsSignificant PAS reduction was observed for all drugs after exposure to 30dyne/cm2 constant shear stress, and all drugs but dipyridamole after exposure to the 30th percentile shear stress waveform of the cfVAD. However, only cilostazol was significantly effective after 70dyne/cm2 constant shear stress exposure, though no significant reduction was observed upon exposure to median shear stress conditions in the cfVAD. These results, coupled with the persistence of reported clinical thrombotic complication, suggest the need for the development of new classes of drugs that are especially designed to mitigate thrombosis in cfVAD patients, while reducing or eliminating the risk of bleeding.

A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells.

BackgroundIn vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery.MethodsThe in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope.ResultsOur results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition.ConclusionThe parallel-plate flow chamber system can well reproduce wall shear stress waveforms acquired from the common carotid artery in resting and immediately after exercise states. Furthermore, it can be used for studying the endothelial cells responses under resting and exercise-induced wall shear stress environments in vitro.

Fatigue strength of SS400 steel under non-proportional loading

This study discusses fatigue properties of low carbon steel, type SS400 steel, under non-proportional loading. Multiaxial fatigue tests under proportional and non-proportional loading conditions with various stress amplitudes were carried out using a hollow cylinder specimen at room temperature. In the test, three types of stress paths were employed. They are a push-pull, a reversed torsion and a circle loading. The circle loading is a cyclic loading combined the push-pull and the reversed torsion loading in which axial and shear stress waveforms have 90 degrees phase differences. From the obtained test results, poor evaluations of failure life under non-proportional loading are indicated when the life is correlated by the equivalent strain range based on von Mises ??eq and the non-proportional strain range ??NP. A modified strain parameter is presented which can evaluate the failure life in high and low strain levels under non-proportional loading.

Abstract 572: Inhibition of MicroRNA-199a-5p Enhances Perfusion Recovery and Arteriogenesis Following Femoral Arterial Ligation

We have recently reported that a subset of collateral artery segments in the mouse hindlimb are exposed to both a 2-fold increase in shear stress magnitude and reversed flow direction (“reversed” flow) following femoral arterial ligation (FAL). These segments experiencing a reversed flow subsequently undergo a disproportionate amplification of collateral growth (i.e. arteriogenesis) after FAL. Interestingly, a subset of microRNAs, including miR-199a-5p, are significantly down-regulated in endothelial cells exposed to a shear stress waveform biomimetic of this pro-arteriogenic “reversed flow” condition in-vitro. Here, we hypothesized that the inhibition of miR-199a-5p would lead to enhanced arteriogenesis and/or perfusion recovery following arterial occlusion. To test this hypothesis, Balb/c mice were treated with either anti-miR-199a-5p or non-targeting control locked-nucleic acid (LNA) immediately following FAL. Treatment efficacy was determined via RT-PCR for expression of miR-199a-5p and its downstream targets’ expression. Laser Doppler perfusion imaging and both whole mount and cross-sectional analysis of vascular casted gracilis muscles were used to assess vascular remodeling. We found that anti-miR-199a-5p LNA markedly reduced miR-199a-5p expression in the gracilis muscle by over 80%, 7 days post-FAL (n=4). By day 21 post-FAL, perfusion recovery was significantly improved in anti-miR-199a-5p treated mice (101.5±1.8% vs. 87.8±1.8%, p≤0.05, n=6). Moreover, both lumenal diameter (106.5±7.2μm vs. 78.4±2.9 μm, p≤0.0001, n=6) and wall area (1770±147μm 2 vs. 1163±41μm 2 , p≤0.0001, n=6) were significantly enhanced in anti-miR-199a-5p treated mice compared to controls. We therefore conclude that the inhibition of miR-199a-5p leads to enhanced perfusion recovery and arteriogenesis following arterial occlusion and could represent a novel strategy for therapeutic arteriogenesis.

Design of a cone-and-plate device for controlled realistic shear stress stimulation on endothelial cell monolayers.

Endothelial cells are constantly exposed to blood flow and the resulting frictional force, the wall shear stress, varies in magnitude and direction with time, depending on vasculature geometry. Previous studies have shown that the structure and function of endothelial cells, and ultimately of the vessel wall, are deeply affected by the nature of wall shear stress waveforms. To investigate the in vitro effects of these stimuli, we developed a compact, programmable, real-time operated system based on cone-and-plate geometry, that can be used within a standard cell incubator. To verify the capability to replicate realistic shear stress waveforms, we calculated both analytically and numerically to what extent the system is able to correctly deliver the stimuli defined by the user at plate level. Our results indicate that for radii greater than 25mm, the shear stress is almost uniform and directly proportional to cone rotation velocity. We further established that using a threshold of 10Hz of wall shear stress waveform frequency components, oscillating flow conditions can be reproduced on cell monolayer surface. Finally, we verified the capability of the system to perform long-term flow exposure experiments ensuring sterility and cell culture viability on human umbilical vein endothelial cells exposed to unidirectional and oscillating shear stress. In conclusion, the system we developed is a highly dynamic, easy to handle, and able to generate pulsatile and unsteady oscillating wall shear stress waveforms. This system can be used to investigate the effects of realistic stimulations on endothelial cells, similar to those exerted in vivo by blood flow.

Microfluidic emulation of mechanical circulatory support device shear-mediated platelet activation.

Thrombosis of ventricular assist devices (VADs) compromises their performance, with associated risks of systemic embolization, stroke, pump stop and possible death. Anti-thrombotic (AT) drugs, utilized to limit thrombosis, are largely dosed empirically, with limited testing of their efficacy. Further, such testing, if performed, typically examines efficacy under static conditions, which is not reflective of actual shear-mediated flow. Here we adopted our previously developed Device Thrombogenicity Emulation methodology to design microfluidic platforms able to emulate representative shear stress profiles of mechanical circulatory support (MCS) devices. Our long-term goal is to utilize these systems for point-of-care (POC) personalized testing of AT efficacy under specific, individual shear profiles. First, we designed different types of microfluidic channels able to replicate sample shear stress patterns observed in MCS devices. Second, we explored the flexibility of microfluidic technology in generating dynamic shear stress profiles by modulating the geometrical features of the channels. Finally, we designed microfluidic channel systems able to emulate the shear stress profiles of two commercial VADs. From CFD analyses, the VAD-emulating microfluidic systems were able to replicate the main characteristics of the shear stress waveforms of the macroscale VADs (i.e., shear stress peaks and duration). Our results establish the basis for development of a lab-on-chip POC system able to perform device-specific and patient-specific platelet activation state assays.

Endothelial cell activation by hemodynamic shear stress derived from arteriovenous fistula for hemodialysis access

Intimal hyperplasia (IH) is the first cause of failure of an arteriovenous fistula (AVF). The aim of the present study was to investigate the effects on endothelial cells (ECs) of shear stress waveforms derived from AVF areas prone to develop IH. We used a cone-and-plate device to obtain real-time control of shear stress acting on EC cultures. We exposed human umbilical vein ECs for 48 h to different shear stimulations calculated in a side-to-end AVF model. Pulsatile unidirectional flow, representative of low-risk stenosis areas, induced alignment of ECs and actin fiber orientation with flow. Shear stress patterns of reciprocating flow, derived from high-risk stenosis areas, did not affect EC shape or cytoskeleton organization, which remained similar to static cultures. We also evaluated flow-induced EC expression of genes known to be involved in cytoskeletal remodeling and expression of cell adhesion molecules. Unidirectional flow induced a significant increase in Kruppel-like factor 2 mRNA expression, whereas it significantly reduced phospholipase D1, α4-integrin, and Ras p21 protein activator 1 mRNA expression. Reciprocating flow did not increase Kruppel-like factor 2 mRNA expression compared with static controls but significantly increased mRNA expression of phospholipase D1, α4-integrin, and Ras p21 protein activator 1. Reciprocating flow selectively increased monocyte chemoattractant protein-1 and IL-8 production. Furthermore, culture medium conditioned by ECs exposed to reciprocating flows selectively increased smooth muscle cell proliferation compared with unidirectional flow. Our results indicate that protective vascular effects induced in ECs by unidirectional pulsatile flow are not induced by reciprocating shear forces, suggesting a mechanism by which oscillating flow conditions may induce the development of IH in AVF and vascular access dysfunction.

Hemodynamic transition driven by stent porosity in sidewall aneurysms

The healing process of intracranial aneurysms (IAs) treated with flow diverter stents (FDSs) depends on the IA flow modifications and on the epithelization process over the neck. In sidewall IA models with straight parent artery, two main hemodynamic regimes with different flow patterns and IA flow magnitude were broadly observed for unstented and high porosity stented IA on one side, and low porosity stented IA on the other side. The hemodynamic transition between these two regimes is potentially involved in thrombosis formation. In the present study, CFD simulations and multi-time lag (MTL) particle imaging velocimetry (PIV) measurements were combined to investigate the physical nature of this transition. Measurable velocity fields and non-measurable shear stress and pressure fields were assessed experimentally and numerically in the aneurysm volume in the presence of stents with various porosities. The two main regimes observed in both PIV and CFD showed typical flow features of shear and pressure driven regimes. In particular, the waveform of the averaged IA velocities was matching both the shear stress waveform at IA neck or the pressure gradient waveform in parent artery. Moreover, the transition between the two regimes was controlled by stent porosity: a decrease of stent porosity leads to an increase (decrease) of pressure differential (shear stress) through IA neck. Finally, a good PIV–CFD agreement was found except in transitional regimes and low motion eddies due to small mismatch of PIV–CFD running conditions.

A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch.

Background. Compliance mismatch is a negative factor and it needs to be considered in arterial bypass grafting. Objective. A computational model was employed to investigate the effects of arterial compliance mismatch on blood flow, wall stress, and deformation. Methods. The unsteady blood flow was assumed to be laminar, Newtonian, viscous, and incompressible. The vessel wall was assumed to be linear elastic, isotropic, and incompressible. The fluid-wall interaction scheme was constructed using the finite element method. Results. The results show that there are identical wall shear stress waveforms, wall stress, and strain waveforms at different locations. The comparison of the results demonstrates that wall shear stresses and wall strains are higher while wall stresses are lower at the more compliant section. The differences promote the probability of intimal thickening at some locations. Conclusions. The model is effective and gives satisfactory results. It could be extended to all kinds of arteries with complicated geometrical and material factors.

Endothelium exposed to atheroprone flow promotes monocyte transmigration and specification

Atherosclerosis and its consequences, myocardial infarction and stroke continue to be the leading cause of mortality worldwide. Despite recent progress in our understanding of the initiation and progression of atherosclerosis, there is an increasing need to identify novel signaling pathways with potential therapeutic targeting. One of the earliest events in atherogenesis is endothelial dysfunction triggered by disturbed flow characteristic of atherosclerosis susceptible regions. This event is followed by monocyte transmigration and differentiation into macrophages. To mechanistically dissect the contribution of atheroprone flow on the endothelial cell phenotype and monocyte transmigration and specification, we have developed a novel in vitro model in which endothelial cells (EC) are seeded on a collagen gel and exposed to athero‐prone and ‐protective shear stress waveforms. Using this model, we have demonstrated that atheroprone but not atheroprotective flow promotes monocyte recruitment via a Krüppel Like Factor‐2‐dependent pathway. Furthermore, we have documented that transmigrated monocytes under atheroprone flow polarize toward a pro‐inflammatory phenotype as measured by gene expression of a set of pro‐inflammatory markers. This work supports the hypothesis that the hemodynamic environment promotes EC‐monocyte interactions, which are a key determinant of macrophage polarization.

WITHDRAWN: A Fast Method to Estimate the Wall Shear Stress Waveform in Arteries

Withdrawal Notice DOI: 10.1177/1742271X1302100105 Xin Yang, Lyam Hollis, Fiona Adams, Faisel Khan, Peter R Hoskins. A Fast Method to Estimate the Wall Shear Stress Waveform in Arteries. Ultrasound. 2013; 21(1): 23–28. Article withdrawn by publisher. This article was accidentally published twice in the online version of Volume 21 Issue 1, with different DOIs but the same page numbers. There was no duplication of the article in the printed version of Volume 21 Issue 1. The incorrect version of the article with DOI: 10.1177/1742271X1302100105 has been replaced with this correction notice. The correct and citable version of the article remains: Xin Yang, Lyam Hollis, Fiona Adams, Faisel Khan, Peter R Hoskins. A Fast Method to Estimate the Wall Shear Stress Waveform in Arteries. Ultrasound. 2013; 21(1): 23–28. 10.1177/1742271X12473871

Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells

The endothelial glycocalyx, a glycosaminoglycan layer located on the apical surface of vascular endothelial cells, has been shown to be important for several endothelial functions. Previous studies have documented that the glycocalyx is highly abundant in the mouse common carotid region, where the endothelium is exposed to laminar shear stress, and it is resistant to atherosclerosis. In contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus region, an area exposed to nonlaminar shear stress and highly susceptible to atherosclerosis. On the basis of these observations, we hypothesized that the expression of components of the endothelial glycocalyx is differentially regulated by distinct hemodynamic environments. To test this hypothesis, human endothelial cells were exposed to shear stress waveforms characteristic of atherosclerosis-resistant or atherosclerosis-susceptible regions of the human carotid, and the expression of several components of the glycocalyx was assessed. These experiments revealed that expression of several components of the endothelial glycocalyx is differentially regulated by distinct shear stress waveforms. Interestingly, we found that heparan sulfate expression is increased and evenly distributed on the apical surface of endothelial cells exposed to the atheroprotective waveform and is irregularly present in cells exposed to the atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan, syndecan-1, is also differentially regulated by the two waveforms, and its suppression mutes the atheroprotective flow-induced cell surface expression of heparan sulfate. Collectively, these data link distinct hemodynamic environments to the differential expression of critical components of the endothelial glycocalyx.

Combined effect of advanced glycation end products and physiologically relevant dynamic shear stress on endothelial cell functions

Advanced glycation end products (AGEs) and disturbed shear stress are hallmarks of cardiovascular diseases. Our goal was to evaluate the combined effect of AGEs and physiologically relevant dynamic shear stress on endothelial cell (EC) functions. ECs were exposed to glycated or non‐glycated albumin for up to 5 days. ECs were then subjected to shear stress (SS) waveforms mimicking cardiac flow, stenosis flow and recirculation flow for 1hr. EC morphology, metabolic activity and shear induced actin alignment was observed. Also, the expression of ICAM, tissue factor and thrombomodulin was measured to quantify inflammatory and thrombogenic potential. We hypothesized that the combination of disturbed SS and AGEs would enhance EC responses to mimic endothelial dysfunction. Results indicate that ECs incubated with AGEs and exposed to stenosis SS had an altered actin alignment and structure. EC metabolic activity in the presence of glycated albumin, decreased when exposed to disturbed flow. Inflammatory and thrombogenic potential was also enhanced. Thus, the results indicate that the presence of AGEs severely alters EC function under various pathological SS conditions. Thanks to OCAST for supporting this work.

Microfluidic endothelial cell culture model to replicate disturbed flow conditions seen in atherosclerosis susceptible regions

Atherosclerotic lesions occur non-randomly at vascular niches in bends and bifurcations where fluid flow can be characterized as "disturbed" (low shear stress with both forward and retrograde flow). Endothelial cells (ECs) at these locations experience significantly lower average shear stress without change in the levels of pressure or strain, which affects the local balance in mechanical stresses. Common in vitro models of atherosclerosis focus primarily on shear stress without accounting for pressure and strain loading. To overcome this limitation, we used our microfluidic endothelial cell culture model (ECCM) to achieve accurate replication of pressure, strain, and shear stress waveforms associated with both normal flow seen in straight sections of arteries and disturbed flow seen in the abdominal aorta in the infrarenal segment at the wall distal to the inferior mesenteric artery (IMA), which is associated with high incidence of atherosclerotic lesion formation. Human aortic endothelial cells (HAECs) were cultured within the ECCM under both normal and disturbed flow and evaluated for cell shape, cytoskeletal alignment, endothelial barrier function, and inflammation using immunofluorescence microscopy and flow cytometry. Results clearly demonstrate quantifiable differences between cells cultured under disturbed flow conditions, which are cuboidal with short and randomly oriented actin microfilaments and show intermittent expression of β-Catenin and cells cultured under normal flow. However, in the absence of pro-inflammatory stimulation, the levels of expression of activation markers: intra cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial cell growth factor - receptor 2 (VEGF-R2) known to be involved in the initiation of plaque formation were only slightly higher in HAECs cultured under disturbed flow in comparison to cells cultured under normal flow.

Experimental measurement of dynamic fluid shear stress on the ventricular surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact causes and mechanisms of AV calcification are unclear, although previous studies suggest that mechanical forces play a role. It has been clinically demonstrated that calcification preferentially occurs on the aortic surface of the AV. This is hypothesized to be due to differences in the mechanical environments on the two sides of the valve. It is thus necessary to characterize fluid shear forces acting on both sides of the leaflet to test this hypothesis. The current study is one of two studies characterizing dynamic shear stress on both sides of the AV leaflets. In the current study, shear stresses on the ventricular surface of the AV leaflets were measured experimentally on two prosthetic AV models with transparent leaflets in an in vitro pulsatile flow loop using two-component Laser Doppler Velocimetry (LDV). Experimental measurements were utilized to validate a theoretical model of AV ventricular surface shear stress based on the Womersley profile in a straight tube, with corrections for the opening angle of the valve leaflets. This theoretical model was applied to in vivo data based on MRI-derived volumetric flow rates and valve dimension obtained from the literature. Experimental results showed that ventricular surface shear stress was dominated by the streamwise component. The systolic shear stress waveform resembled a half-sinusoid during systole and peaks at 64-71 dyn/cm(2), and reversed in direction at the end of systole for 15-25ms, and reached a significant negative magnitude of 40-51 dyn/cm(2). Shear stresses from the theoretical model applied to in vivo data showed that shear stresses peaked at 77-92 dyn/cm(2) and reversed in direction for substantial period of time (108-110ms) during late systole with peak negative shear stress of 35-38 dyn/cm(2).

Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. Although exact causes and mechanisms of AV calcification are unclear, previous studies suggest that mechanical forces play a role. Since calcium deposits occur almost exclusively on the aortic surfaces of AV leaflets, it has been hypothesized that adverse patterns of fluid shear stress on the aortic surface of AV leaflets promote calcification. The current study characterizes AV leaflet aortic surface fluid shear stresses using Laser Doppler velocimetry and an in vitro pulsatile flow loop. The valve model used was a native porcine valve mounted on a suturing ring and preserved using 0.15% glutaraldehyde solution. This valve model was inserted in a mounting chamber with sinus geometries, which is made of clear acrylic to provide optical access for measurements. To understand the effects of hemodynamics on fluid shear stress, shear stress was measured across a range of conditions: varying stroke volumes at the same heart rate and varying heart rates at the same stroke volume. Systolic shear stress magnitude was found to be much higher than diastolic shear stress magnitude due to the stronger flow in the sinuses during systole, reaching up to 20 dyn/cm(2) at mid-systole. Upon increasing stroke volume, fluid shear stresses increased due to stronger sinus fluid motion. Upon increasing heart rate, fluid shear stresses decreased due to reduced systolic duration that restricted the formation of strong sinus flow. Significant changes in the shear stress waveform were observed at 90 beats/min, most likely due to altered leaflet dynamics at this higher heart rate. Overall, this study represents the most well-resolved shear stress measurements to date across a range of conditions on the aortic side of the AV. The data presented can be used for further investigation to understand AV biological response to shear stresses.