Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access

It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color-flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center-line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo-Doppler technique.     

Increased Inlet Blood Flow Velocity Predicts Low Wall Shear Stress in the Cephalic Arch of Patients with Brachiocephalic Fistula Access

BackgroundAn autogenous arteriovenous fistula is the optimal vascular access for hemodialysis. In the case of brachiocephalic fistula, cephalic arch stenosis commonly develops leading to access failure. We have hypothesized that a contribution to fistula failure is low wall shear stress resulting from post-fistula creation hemodynamic changes that occur in the cephalic arch.MethodsTwenty-two subjects with advanced renal failure had brachiocephalic fistulae placed. The following procedures were performed at mapping (pre-operative) and at fistula maturation (8–32 weeks post-operative): venogram, Doppler to measure venous blood flow velocity, and whole blood viscosity. Geometric and computational modeling was performed to determine wall shear stress and other geometric parameters. The relationship between hemodynamic parameters and clinical findings was examined using univariate analysis and linear regression.ResultsThe percent low wall shear stress was linearly related to the increase in blood flow velocity (p < 0.01). This relationship was more significant in non-diabetic patients (p < 0.01) than diabetic patients. The change in global measures of arch curvature and asymmetry also evolve with time to maturation (p < 0.05).ConclusionsThe curvature and hemodynamic changes during fistula maturation increase the percentage of low wall shear stress regions within the cephalic arch. Low wall shear stress may contribute to subsequent neointimal hyperplasia and resultant cephalic arch stenosis. If this hypothesis remains tenable with further studies, ways of protecting the arch through control of blood flow velocity may need to be developed.     

Effects of wall distensibility in hemodynamic simulations of an arteriovenous fistula

Arteriovenous fistulae are created surgically to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is in part a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. The current study presents fluid–structure interaction (FSI) simulations of a patient-specific model of a mature arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are compared with previously published data of the same model but with rigid walls. Ultrasound-derived wall motion measurements are also used to validate the FSI simulations of the wall motion. Very large time-averaged shear stresses, 10–15 Pa, are calculated at the fistula anastomosis in the FSI simulations, values which are much larger than what is typically thought to be the normal homeostatic shear stress in the peripheral vasculature. Although this result is systematically lower by as much as 50 % compared to the analogous rigid-walled simulations, the inclusion of distensible vessel walls in hemodynamic simulations does not reduce the high anastomotic shear stresses to “normal” values. Therefore, rigid-walled analyses may be acceptable for identifying high shear regions of arteriovenous fistulae.     

Nitric Oxide Resistance Reduces Arteriovenous Fistula Maturation in Chronic Kidney Disease in Rats

Background

Autologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. Chronic kidney disease (CKD) is associated with oxidative stress that can disturb NO-signaling. Here, we evaluated the influence of CKD on AV fistula maturation and NO-signaling.

Methods

CKD was established in rats by a 5/6^th nephrectomy and after 6 weeks, an AV fistula was created between the carotid artery and jugular vein, which was followed up at 3 weeks with ultrasound and flow assessments. Vessel wall histology was assessed afterwards and vasoreactivity of carotid arteries was studied in a wire myograph. The soluble guanylate cyclase (sGC) activator BAY 60–2770 was administered daily to CKD animals for 3 weeks to enhance fistula maturation.

Results

CKD animals showed lower flow rates, smaller fistula diameters and increased oxidative stress levels in the vessel wall. Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in CKD vessels, indicating NO resistance of the NO-receptor sGC. This was confirmed by stimulation with BAY 60–2770 resulting in increased vasorelaxation in CKD vessels. Oral administration of BAY 60–2770 to CKD animals induced larger fistula diameters, however; flow was not significantly different from vehicle-treated CKD animals.

Conclusions

CKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60–2770 could offer therapeutic potential to increase AV fistula maturation.     

The Role of Shear Stress in Arteriovenous Fistula Maturation and Failure: A Systematic Review

Introduction

Non-maturation and post-maturation venous stenosis are the primary causes of failure within arteriovenous fistulae (AVFs). Although the exact mechanisms triggering failure remain unclear, abnormal hemodynamic profiles are thought to mediate vascular remodelling and can adversely impact on fistula patency.

Aim

The review aims to clarify the role of shear stress on outward remodelling during maturation and evaluate the evidence supporting theories related to the localisation and development of intimal hyperplasia within AVFs.

Methods

A systematic review of studies comparing remodelling data with hemodynamic data obtained from computational fluid dynamics of AVFs during and after maturation was conducted.

Results

Outward remodelling occurred to reduce or normalise the level of shear stress over time in fistulae with a large radius of curvature (curved) whereas shear stress was found to augment over time in fistulae with a small radius of curvature (straight) coinciding with minimal to no increases in lumen area. Although this review highlighted that there is a growing body of evidence suggesting low and oscillating shear stress may stimulate the initiation and development of intimal medial thickening within AVFs. Further lines of evidence are needed to support the disturbed flow theory and outward remodelling findings before surgical configurations and treatment strategies are optimised to conform to them. This review highlighted that variation between the time of analysis, classification of IH, resolution of simulations, data processing techniques and omission of various shear stress metrics prevented forming pooling of data amongst studies.

Conclusion

Standardised measurements and data processing techniques are needed to comprehensively evaluate the relationship between shear stress and intimal medial thickening. Advances in image acquisition and flow quantifications coupled with the increasing prevalence of longitudinal studies commencing from fistula creation offer viable techniques and strategies to robustly evaluate the relationship between shear stress and remodelling during maturation and thereafter.     

Direct numerical simulation of transitional flow in a patient-specific intracranial aneurysm

In experiments turbulence has previously been shown to occur in intracranial aneurysms. The effects of turbulence induced oscillatory wall stresses could be of great importance in understanding aneurysm rupture. To investigate the effects of turbulence on blood flow in an intracranial aneurysm, we performed a high resolution computational fluid dynamics (CFD) simulation in a patient specific middle cerebral artery (MCA) aneurysm using a realistic, pulsatile inflow velocity. The flow showed transition to turbulence just after peak systole, before relaminarization occurred during diastole. The turbulent structures greatly affected both the frequency of change of wall shear stress (WSS) direction and WSS magnitude, which reached a maximum value of 41.5Pa. The recorded frequencies were predominantly in the range of 1-500Hz. The current study confirms, through properly resolved CFD simulations that turbulence can occur in intracranial aneurysms.     

Post-stenotic core flow behavior in pulsatile flow and its effects on wall shear stress

Arteries of several species, including man, tend to adjust their diameters such that the mean wall shear stress is in the range of 10-20 dynes cm-2. Additionally, intimal thickening in the human carotid bifurcation correlates well with the reciprocal of wall shear stress as determined in model studies. The correlation indicates that wherever the local mean wall shear stress exceeds approximately 10 dynes cm-2, the artery tends to be spared from intimal thickening. However, it is not known whether mean shear stress, i.e. the time-averaged value, or the instantaneous shear stress is the appropriate correlative variable. Each of these variables suggests different mechanisms for the reaction of the artery wall to its hemodynamic environment. It is therefore important to devise means by which the effects of mean shear and pulsatile shear can be separated in the study of atherogenesis. The present investigation examines the post-stenotic flow field in Plexiglas models under pulsatile conditions approximating those in the aortas of the cynomolgus monkey, an animal often employed in atherogenesis research. Behavior of the core flow and its effects on wall shear stress are studied for stenoses of 75 and 90% area reductions using laser velocimetry. The results show that the post-stenotic field contains regions in which the mean wall shear stress is low, but the pulsatile excursions are large.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative contribution of wall shear stress and injury in experimental intimal thickening at PTFE end-to-side arterial anastomoses

BACKGROUND: Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. METHODS AND RESULTS: The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. CONCLUSIONS: The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.     

Numerical modeling of pulsatile turbulent flow in stenotic vessels

Pulsatile turbulent flow in stenotic vessels has been numerically modeled using the Reynolds-averaged Navier-Stokes equation approach. The commercially available computational fluid dynamics code (CFD), FLUENT, has been used for these studies. Two different experiments were modeled involving pulsatile flow through axisymmetric stenoses. Four different turbulence models were employed to study their influence on the results. It was found that the low Reynolds number k-omega turbulence model was in much better agreement with previous experimental measurements than both the low and high Reynolds number versions of the RNG (renormalization-group theory) k-epsilon turbulence model and the standard k-epsilon model, with regard to predicting the mean flow distal to the stenosis including aspects of the vortex shedding process and the turbulent flow field. All models predicted a wall shear stress peak at the throat of the stenosis with minimum values observed distal to the stenosis where flow separation occurred.     

Flow in the well: computational fluid dynamics is essential in flow chamber construction

A perfusion system was developed to generate well defined flow conditions within a well of a standard multidish. Human vein endothelial cells were cultured under flow conditions and cell response was analyzed by microscopy. Endothelial cells became elongated and spindle shaped. As demonstrated by computational fluid dynamics (CFD), cells were cultured under well defined but time varying shear stress conditions. A damper system was introduced which reduced pulsatile flow when using volumetric pumps. The flow and the wall shear stress distribution were analyzed by CFD for the steady and unsteady flow field. Usage of the volumetric pump caused variations of the wall shear stresses despite the controlled fluid environment and introduction of a damper system. Therefore the use of CFD analysis and experimental validation is critical in developing flow chambers and studying cell response to shear stress. The system presented gives an effortless flow chamber setup within a 6-well standard multidish.     

Flush-mounted hot film anemometer accuracy in pulsatile flow

The accuracy of a flush-mounted hot film anemometer probe for wall shear stress measurements in physiological pulsatile flows was evaluated in fully developed pulsatile flow in a rigid straight tube. Measured wall shear stress waveform based on steady flow anemometer probe calibrations were compared to theoretical wall shear stress waveforms based on well-established theory and measured flow rate waveforms. The measured and theoretical waveforms were in close agreement during systole (average deviation of 14 percent at peak systole). As expected, agreement was poor during diastole because of flow reversal and diminished frequency response at low shear rate.     

Phasic flow patterns at a hemodialysis venous anastomosis

A phase-by-phase analysis of local flow patterns at the venous anastomosis of an arteriovenous hemodialysis angioaccess loop graft (AVLG) was made. The study was carried out in an elastic, transparent Silastic in vitro flow model, which duplicates the detail geometry of the AVLG obtained from an animal model (30+ kg dogs with 12 weeks bilateral femoral AVLG implantation). The flow model was installed in a mock pulsatile flow loop system designed to simulate physiological conditions. Flow visualization was made in laser-illuminated flow fields using a high-speed cine camera. Analysis of the high-speed cine indicates there is a distinct separation region downstream of the anastomotic toe in the median plane and a stagnation region that oscillates along the opposite wall. During inward motion of the vessel wall, accumulation of particles in the separation region and the nearby stagnation region is observed. A large swirl appears in the distal vein during end-systolic period. A double-helical flow pattern occurs further down in the distal vein. Retrograde flow in the distal vein occurs in an "oscillating" manner following each cardiac cycle.     

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

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.     

Pressure drop and flow rate measurements in a human aortic bifurcation cast for steady and pulsatile flow

Pressure drop and flow rate measurements in a rigid cast of a human aortic bifurcation under both steady and physiological pulsatile flow conditions are reported. Integral momentum and mechanical energy balances are used to calculate impedance, spatially averaged wall shear stress and viscous dissipation rate from the data. In the daughter branches, steady flow impedance is within 30% of the Poiseuille flow prediction, while pulsatile flow impedance is within a factor of 2 of fully developed, oscillatory, straight tube flow theory (Womersley theory). Estimates of wall shear stress are in accord with measurements obtained from velocity profiles. Mean pressure drop and viscous dissipation rate are elevated in pulsatile flow relative to steady flow at the mean flow rate, and the exponents of their Reynolds number dependence are in accord with available theory.     

Pulsatile poststenotic flow studies with laser Doppler anemometry

The pulsatile flow field distal to axisymmetric constrictions in a straight tube was studied using laser Doppler anemometry. The upstream centerline velocity waveform was sinusoidal at a frequency parameter of 7.5 and mean Reynolds number of 600. Stenosis models of 25, 50 and 75% area reduction were employed and velocity data were derived by ensemble averaging methods. Extensive measurements of the pulsatile velocity profiles are reported, and wall shear rates were computed from the near wall velocity profile gradients. The experiments indicate that a permanent region of poststenotic flow separation does not exist even for the severest constriction, in contrast to results for steady flow. Values of wall shear stress were greatest near the throat of the constriction and were relatively low in the poststenotic region, including the region of most intense flow disturbance. Turbulence was found only for the 75% stenosis model and was created only during a segment of the cycle. Although much emphasis has been placed upon turbulence in the detection of arterial stenoses, particularly as identified by Doppler ultrasound spectral broadening, the present study implies that identification of flow disturbances of an organized nature may be more fundamental in recognizing mild to moderate disease. Additionally, the relationship of these flow field results to the animal aortic coarctation model often employed in atherogenesis studies is discussed.     

Wall shear stresses remain elevated in mature arteriovenous fistulas: a case study

Maintaining vascular access (VA) patency continues to be the greatest challenge for dialysis patients. VA dysfunction, primarily due to venous neointimal hyperplasia development and stenotic lesion formation, is mainly attributed to complex hemodynamics within the arteriovenous fistula (AVF). The effect of VA creation and the subsequent geometrical remodeling on the hemodynamics and shear forces within a mature patient-specific AVF is investigated. A 3D reconstructed geometry of a healthy vein and a fully mature patient-specific AVF was developed from a series of 2D magnetic resonance image scans. A previously validated thresholding technique for region segmentation and lumen cross section contour creation was conducted in MIMICS 10.01, allowing for the creation of a 3D reconstructed geometry. The healthy vein and AVF computational models were built, subdivided, and meshed in GAMBIT 2.3. The computational fluid dynamic (CFD) code FLUENT 6.3.2 (Fluent Inc., Lebanon, NH) was employed as the finite volume solver to determine the hemodynamics and shear forces within the healthy vein and patient-specific AVF. Geometrical alterations were evaluated and a CFD analysis was conducted. Substantial geometrical remodeling was observed, following VA creation with an increase in cross-sectional area, out of plane curvature (maximum angle of curvature in AVF=30?deg), and angle of blood flow entry. The mean flow velocity entering the vein of the AVF is dramatically increased. These factors result in complex three-dimensional hemodynamics within VA junction (VAJ) and efferent vein of the AVF. Complex flow patterns were observed and the maximum and mean wall shear stress (WSS) magnitudes are significantly elevated. Flow reversal was found within the VAJ and efferent vein. Extensive geometrical remodeling during AVF maturation does not restore physiological hemodynamics to the VAJ and venous conduit of the AVF, and high WSS and WSS gradients, and flow reversal persist. It is theorized that the vessel remodelling and the continued non-physiological hemodynamics within the AVF compound to result in stenotic lesion development.     

Pulsatile flow in fusiform models of abdoiminal aortic aneurysms: flow fields, velocity patterns and flow-induced wall stresses

As one important step in the investigation of the mechanical factors that lead to rupture of abdominal aortic aneurysms, flow fields and flow-induced wall stress distributions have been investigated in model aneurysms under pulsatile flow conditions simulating the in vivo aorta at rest. Vortex pattern emergence and evolution were evaluated, and conditions for flow stability were delineated. Systolic flow was found to be forward-directed throughout the bulge in all the models, regardless of size. Vortices appeared in the bulge initially during deceleration from systole, then expanded during the retrograde flow phase. The complexity of the vortex field depended strongly on bulge diameter In every model, the maximum shear stress occurred at peak systole at the distal bulge end, with the greatest shear stress developing in a model corresponding to a 4.3 cm AAA in vivo. Although the smallest models exhibited stable flow throughout the cycle, flow in the larger models became increasingly unstable as bulge size increased, with strong amplification of instability in the distal half of the bulge. These data suggest that larger aneurysms in vivo may be subject to more frequent and intense turbulence than smaller aneurysms. Concomitantly, increased turbulence may contribute significantly to wall stress magnitude and thereby to risk of rupture.     

Transient blood flow in elastic coronary arteries with varying degrees of stenosis and dilatations: CFD modelling and parametric study

In this paper, we have analysed pulsatile flow through partially occluded elastic arteries, to determine the haemodynamic parameters of wall shear stress (WSS), wall pressure gradient and pressure drops (ΔP), contributing to enhanced flow resistance and myocardial ischaemic regions which impair cardiac contractility and cause increased work load on the heart. In summary, it can be observed that stenoses in an artery significantly influence the haemodynamic parameters of wall shear stress and pressure drop in contrast to dilatations case. This deduces that stenosis plays a more critical role in plaque growth and vulnerability in contrast to dilatation, and should be the key element in cardiovascular pathology and diagnosis. Through quantitative analysis of WSS and ΔP, we have provided a clearer insight into the haemodynamics of atherosclerotic arteries. Determination of these parameters can be helpful to cardiologists, because it is directly implicated in the genesis and development of atherosclerosis.     

Experimental technique of measuring 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. 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 (<5 dyn/cm2) but elevated to its peak during mid to late systole at about 18-20 dyn/cm2. Low magnitude shear stress (<5 dyn/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.     

Flow-induced wall shear stress in abdominal aortic aneurysms: Part II--pulsatile flow hemodynamics

In continuing the investigation of AAA hemodynamics, unsteady flow-induced stresses are presented for pulsatile blood flow through the double-aneurysm model described in Part I. Physiologically realistic aortic blood flow is simulated under pulsatile conditions for the range of time-average Reynolds numbers 50< or =Re(m) < or =300. Hemodynamic disturbance is evaluated for a modified set of indicator functions which include wall pressure (p(w)), wall shear stress (tau(w)), Wall Shear Stress Gradient (WSSG), time-average wall shear stress (tau(w)*), and time-average Wall Shear Stress Gradient WSSG*. At peak flow, the highest shear stress and WSSG levels are obtained at the distal end of both aneurysms, in a pattern similar to that of steady flow. The maximum values of wall shear stresses and wall shear stress gradients are evaluated as a function of the time-average Reynolds number resulting in a fourth order polynomial correlation. A comparison between numerical predictions for steady and pulsatile flow is presented, illustrating the importance of considering time-dependent flow for the evaluation of hemodynamic indicators.