Fluid Shear Stress Characteristics of the Ventricular Surface Versus the Aortic Surface of the Aortic Valve: An In Vitro Study

2011 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Aortic Valve Calcification ◽  
Fluid Shear ◽  
Valve Calcification ◽  
Ventricular Surface

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2]. Consequently, it has been proposed that the phenomenon of diseased calcium nodules developing exclusively on the aortic surface as opposed to the ventricular surface is due to the exposure of the aortic surface to disturbed shear stresses, whereas undisturbed shear stresses on the ventricular surface do not trigger calcification [3,4]. Additionally, it has been observed that the non-coronary leaflet of the AV is more susceptible to calcification, which is hypothesized to be due to reduced shear stresses from the lack of diastolic coronary flow [5].

The Congenital Bicuspid Aortic Valve Can Experience Fluid Shear Stresses Associated With Sclerosis

2011 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Swetha Rathan ◽  
Gowthami Tamilselvan ◽  
Nikolay V. Vasilyev ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Ex Vivo ◽  
The Elderly ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Aortic Valve Calcification ◽  
Fluid Shear ◽  
Valve Calcification ◽  
Mechanical Environment ◽  
High Prevalence

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2].

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Steady Flow ◽  
Fluid Shear Stress ◽  
Shear Stresses ◽  
Straight Tube ◽  
Valve Leaflet ◽  
Fluid Shear ◽  
Valve Model

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5dyn/cm2) but elevated to its peak during mid to late systole at about 18–20 dyn/cm2. Low magnitude shear stress (<5dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

scholarly journals FP608SNF472 INHIBITS HUMAN AORTIC VALVE CALCIFICATION IN VITRO

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i247-i247
Author(s):  
Arseny Zabirnyk ◽  
Maria Bogdanova ◽  
Miguel D Ferrer ◽  
Maria Pérez ◽  
Mari-Liis Kaljusto ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Human Aortic Valve

Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium

1992 ◽  
Vol 263 (2) ◽  
pp. C389-C396 ◽  
Author(s):  
A. Malek ◽  
S. Izumo
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Fluid Velocity ◽  
Low Frequency ◽  
Turbulent Shear ◽  
Specific Response ◽  
Dependent Manner ◽  
Fluid Shear ◽  
Endothelin 1

We report here that the level of endothelin-1 (ET-1) mRNA from bovine aortic endothelial cells grown in vitro is rapidly (within 1 h of exposure) and significantly (fivefold) decreased in response to fluid shear stress of physiological magnitude. The downregulation of ET-1 mRNA occurs in a dose-dependent manner that exhibits saturation above 15 dyn/cm2. The decrease is complete prior to detectable changes in endothelial cell shape and is maintained throughout and following alignment in the direction of blood flow. Peptide levels of ET-1 secreted into the media are also reduced in response to fluid shear stress. Cyclical stretch experiments demonstrated no changes in ET-1 mRNA, while increasing media viscosity with dextran showed that the downregulation is a specific response to shear stress and not to fluid velocity. Although both pulsatile and turbulent shear stress of equal time-average magnitude elicited the same decrease in ET-1 mRNA as steady laminar shear (15 dyn/cm2), low-frequency reversing shear stress did not result in any change. These results show that the magnitude as well as the dynamic character of fluid shear stress can modulate expression of ET-1 in vascular endothelium.

scholarly journals A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report

2020 ◽  
Vol 11 ◽  
Author(s):  
Arsenii Zabirnyk ◽  
Maria del Mar Perez ◽  
Marc Blasco ◽  
Kåre-Olav Stensløkken ◽  
Miguel D. Ferrer ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Growth Medium ◽  
Ex Vivo ◽  
Growth Media ◽  
Dependent Manner ◽  
Ex Vivo Model ◽  
Aortic Valves ◽  
Valve Calcification ◽  
Calcium Accumulation ◽  
Aortic Valve Leaflets

Background: No pharmacological treatment exists to prevent or stop the calcification process of aortic valves causing aortic stenosis. The aim of this study was to develop a robust model of induced calcification in whole aortic valve leaflets which could be suitable for studies of the basic mechanisms and for testing potentially inhibitory drugs.Methods: Pig hearts were obtained from a commercial abattoir. The aortic valve leaflets were dissected free and randomized between experimental groups. Whole leaflets were cultured in individual wells. Two growth media were used for cultivation: standard growth medium and an antimyofibroblastic growth medium. The latter was employed to inhibit contraction of the leaflet into a ball-like structure. Calcification was induced in the growth medium by supplementation with an osteogenic medium. Leaflets were cultivated for four weeks and medium was changed every third day. To block calcification, the inhibitor SNF472 (a formulation of the hexasodium salt of myo-inositol hexaphosphate hexasodium salt) was used at concentrations between 1 and 100 µM. After cultivation for four weeks the leaflets were snap frozen in liquid nitrogen and kept at −80 °C until blind assessment of the calcium amount in leaflets by inductively coupled plasma optical emission spectroscopy. For statistical analysis, a Kruskal–Wallis test with Dunn’s post-test was applied.Results: Osteodifferentiation with calcium accumulation was in principle absent when standard medium was used. However, when the antimyofibroblastic medium was used, a strong calcium accumulation was induced (p = 0.006 compared to controls), and this was blocked in a dose-dependent manner by the calcification inhibitor SNF472 (p = 0.008), with an EC50 of 3.3 µM.Conclusion: A model of experimentally induced calcification in cultured whole leaflets from porcine aortic valves was developed. This model can be useful for studying the basic mechanisms of valve calcification and to test pharmacological approaches to inhibit calcification.

Contribution of Hemodynamic Shear Stress Magnitude and Frequency Abnormalities to Calcific Aortic Valve Disease Pathogenesis

2013 ◽  
Author(s):  
Ling Sun ◽  
Philippe Sucosky
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Valve Disease ◽  
Molecular Signaling ◽  
Fluid Shear ◽  
Calcific Aortic Valve Disease ◽  
Hemodynamic Shear Stress

Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between atherogenic risk factors, molecular signaling networks and hemodynamic cues. While our earlier work demonstrated that progressive alterations in fluid shear stress (FSS) on the fibrosa could trigger valvular inflammation [1], the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. Supported by our previous studies, we hypothesize that valve leaflets are sensitive to both WSS magnitude and pulsatility and that abnormalities in either promote CAVD development. This study aims at elucidating ex vivo the contribution of isolated and combined alterations in FSS magnitude and pulsatility to valvular calcification.

scholarly journals The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

2012 ◽  
Vol 303 (6) ◽  
pp. H721-H731 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Nikolai Vasilyev ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
High Frequency ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Flow Loop ◽  
Model Flow ◽  
Image Velocimetry ◽  
Vitro Model

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

scholarly journals Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1366-1374 ◽  
Author(s):  
JL Moake ◽  
NA Turner ◽  
NA Stathopoulos ◽  
L Nolasco ◽  
JD Hellums
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Fluid Shear Stress ◽  
Thrombus Formation ◽  
Adenosine Diphosphate ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Von Willebrand ◽  
Induced Aggregation

Abstract Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large von Willebrand factor (vWF) multimers in the suspending fluid exogenous to the platelets mediates aggregation. Adenosine diphosphate (ADP) is also required and, in these experiments, was released from the platelets subjected to shear stress. At 120 dyne/cm2, the release of endogenous platelet vWF multimers can substitute for exogenous large or unusually large vWF forms in mediating aggregation. Endogenous released platelet vWF forms, as well as exogenous large or unusually large vWF multimers, must bind to both glycoproteins Ib and the IIb/IIIa complex to produce aggregation. Shear- induced aggregation is the result of shear stress alteration of platelet surfaces, rather than of shear effects on vWF multimers. It is mediated by either large plasma-type vWF multimers, endogenous released platelet vWF forms, or unusually large vWF multimers derived from endothelial cells, requires ADP, and is not inhibited significantly by aspirin. This type of aggregation may be important in platelet thrombus formation within narrowed arterial vessels, and may explain the limited therapeutic utility of aspirin in arterial thrombosis.

scholarly journals Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche

2020 ◽  
Author(s):  
Mohammad Haroon ◽  
Jenneke Klein-Nulend ◽  
Astrid D. Bakker ◽  
Jianfeng Jin ◽  
Carla Offringa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Mechanical Forces ◽  
Fluid Shear ◽  
Muscle Stem Cells ◽  
Pulsating Fluid

ABSTRACTBackgroundMuscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forces in vitro but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs.MethodsMuSCs deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles were visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined.ResultsEx vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stress in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels, while nNOS expression was unaltered. Pulsating fluid shear stress enhanced gene expression of c-Fos, Cdk4, and IL-6, while expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged.ConclusionsWe conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation.

scholarly journals Hemodynamics and Mechanobiology of Aortic Valve Inflammation and Calcification

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Kartik Balachandran ◽  
Philippe Sucosky ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Ex Vivo ◽  
Axial Stress ◽  
Biological Response ◽  
Shear Stresses ◽  
Mechanical Stimuli ◽  
Valve Remodeling ◽  
Valve Pathology ◽  
Opening And Closing

Cardiac valves function in a mechanically complex environment, opening and closing close to a billion times during the average human lifetime, experiencing transvalvular pressures and pulsatile and oscillatory shear stresses, as well as bending and axial stress. Although valves were originally thought to be passive pieces of tissue, recent evidence points to an intimate interplay between the hemodynamic environment and biological response of the valve. Several decades of study have been devoted to understanding these varied mechanical stimuli and how they might induce valve pathology. Here, we review efforts taken in understanding the valvular response to its mechanical milieu and key insights gained fromin vitroandex vivowhole-tissue studies in the mechanobiology of aortic valve remodeling, inflammation, and calcification.

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