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.     

The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta

Purpose

The goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples.

Methods

The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens.

Results

The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r² = 0.3099; P = 0.0047).

Conclusion

Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

     

Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability

A better understanding of how hemodynamic factors affect the integrity and function of the vascular endothelium is necessary to appreciate more fully how atherosclerosis is initiated and promoted. A novel technique is presented to assess the relation between fluid dynamic variables and the permeability of the endothelium to macromolecules. Fully anesthetized, domestic swine were intravenously injected with the albumin marker Evans blue dye, which was allowed to circulate for 90 min. After the animals were euthanized, silicone casts were made of the abdominal aorta and its iliac branches. Pulsatile flow calculations were subsequently made in computational regions derived from the casts. The distribution of the calculated time-dependent wall shear stress in the external iliac branches was directly compared on a point-by-point basis with the spatially varying in vivo uptake of Evans blue dye in the same arteries. The results indicate that in vivo endothelial permeability to albumin decreases with increasing time-average shear stress over the normal range. Additionally, endothelial permeability increases slightly with oscillatory shear index.     

Measurement of wall motion and wall shear in a compliant arterial cast

Initial measurements of the time-varying wall shear rate at two sites in a compliant cast of a human aortic bifurcation are presented. The shear rates were derived from flow velocities measured by laser Doppler velocimetry (LDV) near the moving walls of the cast. To derive these shear rate values, the distance from the velocimeter sampling volume to the cast wall must be known. The time variation of this distance was obtained from LDV measurements of the velocity of the wall itself.     

Effects of blood storage on rheology and damage in low-stress shear flow

Data are presented on the rheological and hemolytic behavior of whole human blood as it ages while stored at 4 degrees C (as in blood banking practice) up to 26 days. The viscometric properties of steady shear viscosity eta and oscillatory (complex) viscosity eta * = eta' - i eta" reported over ranges of shear rate gamma and radian frequency omega of 33 less than gamma less than 4130 s-1 and 1.5 less than omega less than 48 s -1; data on autologous plasma are given for reference. The Cox-Merz relation, eta (gamma) = [eta *(omega)] omega = gamma, is found to be a good approximation, with eta greater than or equal to [eta *], over the range studied. Release of hemoglobin (Hgb) and lactate dehydrogenase (LDH) into the plasma during shearing is tracked as a function of time for 30 min, and its sensitivity to gamma magnitude is measured. Bloods from four different donors are studied, with primary attention given to one (SSR). For all bloods, the release of both Hgb and LDH increases with storage age, but differences in such aging characteristics between different bloods can be substantial (even when rheological properties are identical). A post-shear incubation at 4 degrees C for one day shows no enhancement of plasma Hgb and LDH levels beyond those expected from normal aging after the shearing experience, demonstrating the absence of significant delayed-action effects as a consequence of shearing trauma.     

Longitudinal movements and resulting shear strain of the arterial wall

There has been little interest in the longitudinal movement of the arterial wall. It has been assumed that this movement is negligible compared with the diameter change. Using a new high-resolution noninvasive ultrasonic method, we measured longitudinal movements and diameter change of the common carotid artery of 10 healthy humans. During the cardiac cycle, a distinct bidirectional longitudinal movement of the intima-media complex could be observed in all the subjects. An antegrade longitudinal movement, i.e., in the direction of blood flow, in early systole [0.39 mm (SD 0.26)] was followed by a retrograde longitudinal movement, i.e., in the direction opposite blood flow [-0.52 mm (SD 0.27)], later in systole and a second antegrade longitudinal movement [0.41 mm (SD 0.33)] in diastole. The corresponding diameter change was 0.65 mm (SD 0.19). The adventitial region showed the same basic pattern of longitudinal movement; however, the magnitude of the movements was smaller than that of the intima-media complex, thereby introducing shear strain and, thus, shear stress within the wall [maximum shear strain between the intima-media complex and the adventitial region was 0.36 rad (SD 0.26). These phenomena have not previously been described. Measurements were also performed on the abdominal aorta (n = 3) and brachial (n = 3) and popliteal (n = 3) arteries. Our new information seems to be of fundamental importance for further study and evaluation of vascular biology and hemodynamics and, thus, for study of atherosclerosis and vascular diseases.     

Effects of arterial wall stress on vasomotion

Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress. Indeed blood flow induces intraluminal pressure variations and shear stress. An increase in pressure may induce a vessel contraction, a phenomenon known as the myogenic response. Many muscular vessels present vasomotion, i.e., rhythmic diameter oscillations caused by synchronous cytosolic calcium oscillations of the smooth muscle cells. Vasomotion has been shown to be modulated by pressure changes. To get a better understanding of the effect of stress and in particular pressure on vasomotion, we propose a model of a blood vessel describing the calcium dynamics in a coupled population of smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that a rise in pressure increases the calcium concentration. This may either induce or abolish vasomotion, or increase its frequency depending on the initial conditions. In our model the myogenic response is less pronounced for large arteries than for small arteries and occurs at higher values of pressure if the wall thickness is increased. Our results are in agreement with experimental observations concerning a broad range of vessels.     

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background

Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk.

Methods

We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period.

Results

Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50^th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50^th percentile produced significantly lower estimated risks.

Conclusion

RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.     

Correlation between quantitative analysis of wall shear stress and intima-media thickness in atherosclerosis development in carotid arteries

Background

This paper presents quantitative analysis of blood flow shear stress by measuring the carotid arterial wall shear stress (WSS) and the intima-media thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly basis in order to cause atherosclerosis.

Methods

This study is based on establishing an atherosclerosis model of high-fat rabbits, and measuring the rabbits’ common carotid arterial WSS of the experimental group and control group on a weekly basis. Detailed analysis was performed by using WSS quantification.

Results

We have demonstrated small significant difference of rabbit carotid artery WSS between the experimental group and the control group (P<0.01) from the 1st week onwards, while the IMT of experimental group had larger differences from 5th week compared with the control group (P<0.05). Next, we have shown that with increasing blood lipids, the rabbit carotid artery shear stress decreases and the rabbit carotid artery IMT goes up. The decrease of shear stress appears before the start of IMT growth. Furthermore, our receiver operator characteristic (ROC) curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm², the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and the specificity is 81.3%. The area under the ROC curve is 0.9283.

Conclusions

All these data goes to show that WSS decreasing to 1.198 dyne/cm² can be used as an indicator that rabbit common carotid artery comes into the period of fibrous plaques. In conclusion, our study is able to find and confirm that the decrease of the arterial WSS can predict the occurrence of atherosclerosis earlier, and offer help for positive clinical intervention.

     

The effect of compliance on wall shear in casts of a human aortic bifurcation

Rigid and compliant casts of a human aortic bifurcation were subjected to physiologically realistic pulsatile fluid flows. At a number of sites near the wall in the approximate median plane of the bifurcation of these models, fluid velocity was measured with a laser Doppler velocimeter, and wall motion (in the case of the compliant cast) was determined with a Reticon linescan camera. The velocity and wall motion data were combined to estimate the instantaneous shear rates at the cast wall. Analysis showed that at the outer walls the cast compliance reduced shear rates, while at the walls of the flow divider the shear rate was increased.     

Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model

The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.     

Influence of non-Newtonian properties of blood on the wall shear stress in human atherosclerotic right coronary arteries

The objective of this work is to investigate the effect of non-Newtonian properties of blood on the wall shear stress (WSS) in atherosclerotic coronary arteries using both Newtonian and non-Newtonian models. Numerical simulations were performed to examine how the spatial and temporal WSS distributions are influenced by the stenosis size, blood viscosity, and flow rate. The computational results demonstrated that blood viscosity properties had considerable effect on the magnitude of the WSS, especially where disturbed flow was observed. The WSS distribution is highly non-uniform both temporally and spatially, especially in the stenotic region. The maximum WSS occurred at the proximal side of the stenosis, near the outer wall in the curved artery with no stenosis. The lumen area near the inner wall distal to the stenosis region experienced a lower WSS during the entire cardiac cycle. Among the factors of stenosis size, blood viscosity, and flow rate, the size of the stenosis has the most significant effect on the spatial and temporal WSS distributions qualitatively and quantitatively.     

Influence of microbial concentration on the rheology of non-Newtonian fermentation broths

The objective of this study was to quantify the effect of fungal biomass concentration on the rheology of non-Newtonian fermentation systems. Batch fermentations of Penicillium chrysogenum were carried out with glucose as the sole carbon source. The flow behavior of the system was characterized at various fermentation times and was adequately described by the power-law model. The apparent viscosity of the fermentation broth was significantly affected by biomass concentrations in the fermenter. Fermentation broths containing 17.71 g/l biomass as dry weight were characterized by an apparent viscosity of 0.25 Pa s at a shear rate of 50 s⁻¹. Microbial concentration also affected the power-law flow-behavior index and the consistency index. The value of the consistency index ranged from 0.002 Pa s ⁿ at a biomass concentration of 0.1 g/l to 6.14 Pa s ⁿ at a biomass concentration of 17.71 g/l. The flow-behavior index decreased from an initial value of 1 to a final value of 0.17. Simple empirical correlations have been proposed to quantify the dependence of the power-law parameters on fungal biomass concentration. Experimental data obtained in this study were accurately described by these correlations. The general applicability of these relationships was tested, using previously published rheological data on Aspergillus awamori and Aspergillus niger fermentation broths, and good agreement was seen between experimental data and the predictions from the empirical correlations. Received: 24 March 1998 / Received revision: 10 September 1998 / Accepted: 16 October 1998     

A study on the compliance of a right coronary artery and its impact on wall shear stress

A computational model incorporating physiological motion and uniform transient wall deformation of a branchless right coronary artery (RCA) was developed to assess the influence of artery compliance on wall shear stress (WSS). Arterial geometry and deformation were derived from modern medical imaging techniques, whereas the blood flow was solved numerically employing a moving-grid approach using a well-validated in-house finite element code. The simulation results indicate that artery compliance affects the WSS in the RCA heterogeneously, with the distal region mostly experiencing these effects. Under physiological inflow conditions, coronary compliance contributed to phase changes in the WSS time history, without affecting the temporal gradient of the local WSS nor the bounds of the WSS magnitude. Compliance does not cause considerable changes to the topology of WSS vector patterns nor to the localization of WSS minima along the RCA. We conclude that compliance is not an important factor affecting local hemodynamics in the proximal region of the RCA while the influence of compliance in the distal region needs to be evaluated in conjunction with the outflow to the myocardium through the major branches of the RCA.     

The role of intimal hyperplasia in arterial spasm.

It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.     

Acute effects of resistance exercise on arterial compliance.

Decreased central arterial compliance is an emerging risk factor for cardiovascular disease. Resistance training is associated with reductions in the elastic properties of central arteries. Currently, it is not known whether this reduction is from one bout of resistance exercise or from an adaptation to multiple bouts of resistance training. Sixteen healthy sedentary or recreationally active adults (11 men and 5 women, age 27 +/- 1 yr) were studied under parallel experimental conditions on 2 separate days. The order of experiments was randomized between resistance exercise (9 resistance exercises at 75% of 1 repetition maximum) and sham control (seated rest in the exercise room). Baseline hemodynamic values were not different between the two experimental conditions. Carotid arterial compliance (via simultaneous B-mode ultrasound and applanation tonometry) decreased and beta-stiffness index increased (P < 0.01) immediately and 30 min after resistance exercise. Immediately after resistance exercise, carotid systolic blood pressure increased (P < 0.01), although no changes were observed in brachial systolic blood pressure at any time points. These measures returned to baseline values within 60 min after the completion of resistance exercise. No significant changes in these variables were observed during the sham control condition. These results indicate that one bout of resistance exercise acutely decreases central arterial compliance, but this effect is sustained for <60 min after the completion of resistance exercise.     

Effects of left ventricle wall thickness uncertainties on cardiac mechanics

Biomechanics and Modeling in Mechanobiology - Computational models of the heart have reached a level of maturity that enables sophisticated patient-specific simulations and hold potential for...