A Control Systems Approach to Quantify Wall Shear Stress Normalization by Flow-Mediated Dilation in the Brachial Artery

Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMD_v to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMD_v and mFMD_v, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMD_v indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD), the peak to baseline diameter ratio (D_peak/D_base), and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shear_AUC) or with area integrated to peak hyperemia (FMD/shear_{AUC_peak})]. Inter-session and intra-session reproducibilities for pFMD_v, mFMD_v and %FMD were comparable (intra-class correlation coefficients within 0.521–0.677 range). Both pFMD_v and mFMD_v showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001) than the other indices (% given are relative reductions): %FMD (~11%, p≥0.074); D_peak/D_base (~11%, p≥0.074); FMD/shear_{AUC_peak} (~20%, p≥0.016) and FMD/shear_AUC (~38%, p≤0.038). Further analysis indicated that wall shear stress normalization under normal (fasting) conditions is already far from ideal (FMD_v << 1), which (therefore) does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.     

CFD Analysis of Pulsatile Flow and Non-Newtonian Behavior of Blood in Arteries

CFD analysis plays an important role in the area of analysis of blood flow as in-vivo measurements of blood flow is costly and easily not accessible. This paper presents simulation of blood flow in healthy and stenosed coronary artery 2- D models. The simulation was done considering non-Newtonian behavior of blood and pulsatile nature of blood flow which is close to physical scenario. Pressure distribution, velocity distribution and wall shear were examined to understand their effect on Atherosclerosis.     

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.     

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 h Re m h 300. Hemodynamic disturbance is evaluated for a modified set of indicator functions which include wall pressure ( p w ), wall shear stress ( w ), Wall Shear Stress Gradient (WSSG), time-average wall shear stress ( 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.     

In Vitro Shear Stress Measurements Using Particle Image Velocimetry in a Family of Carotid Artery Models: Effect of Stenosis Severity,Plaque Eccentricity,and Ulceration

Atherosclerotic disease, and the subsequent complications of thrombosis and plaque rupture, has been associated with local shear stress. In the diseased carotid artery, local variations in shear stress are induced by various geometrical features of the stenotic plaque. Greater stenosis severity, plaque eccentricity (symmetry) and plaque ulceration have been associated with increased risk of cerebrovascular events based on clinical trial studies. Using particle image velocimetry, the levels and patterns of shear stress (derived from both laminar and turbulent phases) were studied for a family of eight matched-geometry models incorporating independently varied plaque features – i.e. stenosis severity up to 70%, one of two forms of plaque eccentricity, and the presence of plaque ulceration). The level of laminar (ensemble-averaged) shear stress increased with increasing stenosis severity resulting in 2–16 Pa for free shear stress (FSS) and approximately double (4–36 Pa) for wall shear stress (WSS). Independent of stenosis severity, marked differences were found in the distribution and extent of shear stress between the concentric and eccentric plaque formations. The maximum WSS, found at the apex of the stenosis, decayed significantly steeper along the outer wall of an eccentric model compared to the concentric counterpart, with a 70% eccentric stenosis having 249% steeper decay coinciding with the large outer-wall recirculation zone. The presence of ulceration (in a 50% eccentric plaque) resulted in both elevated FSS and WSS levels that were sustained longer (∼20 ms) through the systolic phase compared to the non-ulcerated counterpart model, among other notable differences. Reynolds (turbulent) shear stress, elevated around the point of distal jet detachment, became prominent during the systolic deceleration phase and was widely distributed over the large recirculation zone in the eccentric stenoses.     

Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications

Introduction

In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy.

Material and Methods

To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s^-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values.

Results

The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm^-2). The increase of WSS from 0.15 to 5 dyn.cm^-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm^-2 applied for one hour.

Conclusion

Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm^-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB.     

Influence of the Accuracy of Angiography-Based Reconstructions on Velocity and Wall Shear Stress Computations in Coronary Bifurcations: A Phantom Study

Introduction

Wall shear stress (WSS) plays a key role in the onset and progression of atherosclerosis in human coronary arteries. Especially sites with low and oscillating WSS near bifurcations have a higher propensity to develop atherosclerosis. WSS computations in coronary bifurcations can be performed in angiography-based 3D reconstructions. It is essential to evaluate how reconstruction errors influence WSS computations in mildly-diseased coronary bifurcations. In mildly-diseased lesions WSS could potentially provide more insight in plaque progression.

Materials Methods

Four Plexiglas phantom models of coronary bifurcations were imaged with bi-plane angiography. The lumens were segmented by two clinically experienced readers. Based on the segmentations 3D models were generated. This resulted in three models per phantom: one gold-standard from the phantom model itself, and one from each reader. Steady-state and transient simulations were performed with computational fluid dynamics to compute the WSS. A similarity index and a noninferiority test were used to compare the WSS in the phantoms and their reconstructions. The margin for this test was based on the resolution constraints of angiography.

Results

The reconstruction errors were similar to previously reported data; in seven out of eight reconstructions less than 0.10 mm. WSS in the regions proximal and far distal of the stenosis showed a good agreement. However, the low WSS areas directly distal of the stenosis showed some disagreement between the phantoms and the readers. This was due to small deviations in the reconstruction of the stenosis that caused differences in the resulting jet, and consequently the size and location of the low WSS area.

Discussion

This study showed that WSS can accurately be computed within angiography-based 3D reconstructions of coronary arteries with early stage atherosclerosis. Qualitatively, there was a good agreement between the phantoms and the readers. Quantitatively, the low WSS regions directly distal to the stenosis were sensitive to small reconstruction errors.     

腔隙性和非腔隙脑梗塞患者的血压差异研究

目的:比较腔隙性(LI)与非腔隙性(NLI)脑梗塞患者血压变化,评价血压与腔隙性脑梗塞的相关性。方法:选取在我院住院治疗的249例急性脑梗塞患者,根据不同亚型将患者分为腔隙性脑梗塞组(LI组,n=187)与非腔隙性脑梗塞组(NLI组,n=62),比较两组患者血压差异,采用线性相关分析与cox相关分析评估血压与脑梗塞及其危险因素的相关性。结果:LI组患者入院3天收缩压、舒张压显著高于NLI患者组,差异有统计学意义(分别P=0.003,P=0.009);线性回归分析表明,入院时收缩压、入院第3天收缩压、入院第3天舒张压与LI显著相关(均P0.05);cox单因素与多因素分析表明,入院第3天收缩压与LI显著相关(分别P=0.009与P=0.006),与其他协变量不相关(均P0.05)。而患者出院时血压与m RS或NIHSS不相关(分别P=0.788和P=0.898)。结论:与相同严重程度NLI患者比较,LI患者高血压与LI独立相关。LI患者血压显著高于NLI患者,二者差异虽与临床疾病严重程度无关,但很可能是患者发生急性脑梗塞的根本原因。     

高血压患者血压控制水平、血脂水平及颈动脉斑块与冠脉病变的关系

目的:探讨血压控制水平、血脂水平和颈动脉斑块与高血压患者冠脉病变程度和病变支数的关系。方法:回顾性分析2014年01月至2016年05月收住于南京中医药大学附属江苏省中西医结合医院心血管科的原发性高血压患者273例,按血压控制水平分为达标组和未达标组。按颈动脉超声结果判断有无斑块,冠状动脉造影结果使用Gensini评分和病变支数表示,并检测血脂指标。结果:血压控制达标者130人(47.61%),颈动脉有斑块者193例(70.70%)。与血压控制达标患者相比,血压控制不达标者冠脉病变支数及冠脉狭窄程度得分均明显增加(P0.05)。血压不达标合并斑块患者冠脉病变支数和狭窄程度与血压达标无斑块、血压达标合并斑块及血压不达标无斑块患者相比均明显增加(P0.001)。患者HDL-C水平与冠状动脉狭窄程度呈负相关(r=-0.139,P=0.022),AI与冠状动脉狭窄程度呈正相关(r=0.136,P=0.025),LDL/HDL-C和AI与冠脉病变支数均呈正相关,分别为(r=0.128,P=0.035)和(r=0.137,P=0.023)。结论:血压控制不佳,高血脂和颈动脉斑块形成可增加高血压患者冠脉病变的严重程度。     

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures,Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.     

The Association between Within-Visit Blood Pressure Variability and Carotid Artery Atherosclerosis in General Population

Objectives

To determine whether within-visit blood pressure (BP) variability based on three measurements over minutes is associated with increased carotid intima-media thickness (IMT) and plaque in a general population.

Methods

A cross-sectional survey was performed in 2007, and a total of 1222 Beijing community residents aged 50–79 years belonging to part of the Chinese Multi-Provincial Cohort Study (CMCS) were recruited in this study. BP was measured three times at 5-minute intervals during a single visit, and the maximum absolute difference (MAD) between any two readings of three measurements was used to indicate within-visit BP variability. Carotid IMT and plaque scanned by B-mode ultrasound were identified as the surrogate end points in the intermediate stage of atherosclerosis.

Results

After adjustment for established cardiovascular risk factors, the odds ratio (OR) (95% confidence interval (CI)) for increased carotid IMT and internal carotid plaque associated with the highest within-visit diastolic BP (DBP) variability (MAD > mean + standard deviation (SD)) compared with participants in the lowest within-visit DBP variability (MAD ≤ mean −SD) was 4.92 (1.48–16.42) and 6.07 (1.31–28.10), respectively, in the normotensives (P = 0.01; P = 0.02). The OR (95% CI) for internal carotid plaque associated with the highest within-visit systolic BP (SBP) variability (MAD >mean +SD) compared with participants in the lowest within-visit SBP variability (MAD ≤ mean −SD) was 3.54 (1.26–10.00) in the hypertensives on antihypertensive therapy (P = 0.02).

Conclusions

Within-visit DBP variability was associated with increased carotid IMT and internal carotid plaque in the normotensive population, and within-visit SBP variability was associated with internal carotid plaque in hypertensive patients undergoing antihypertensive therapy.     

Determination of Micronutrients and Oxidative Stress Status in the Blood of STZ-Induced Experimental Diabetic Rat Models

This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3–4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p < 0.005). Retinol levels decreased significantly in STZ groups (p < 0.005). In the groups administered 55 mg/kg STZ ferrum and vitamin C levels were found significantly lower than the other groups (p < 0.005). In the group given 65 mg/kg STZ α-tocopherol levels were highest (p < 0.005) among other groups. There was not any difference between the groups for MDA, Cu/Zn, and Mg. For both doses, oxidative stress status was not significantly affected within 48 h of the application, however, some micronutritents were affected significantly.     

Characterizaton of the Vessel Geometry,Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

Introduction

Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5).

Methods

Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics.

Results

In normal mouse fetuses between E14.5–18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here.

Conclusion

Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.     

Select de novo Gene and Protein Expression During Renal Epithelial Cell Culture in Rotating Wall Vessels is Shear Stress Dependent

The rotating wall vessel has gained popularity as a clinical cell culture tool to produce hormonal implants. It is desirable to understand the mechanisms by which the rotating wall vessel induces genetic changes, if we are to prolong the useful life of implants. During rotating wall vessel culture gravity is balanced by equal and opposite hydrodynamic forces including shear stress. The current study provides the first evidence that shear stress response elements, which modulate gene expression in endothelial cells, are also active in epithelial cells. Rotating wall culture of renal cells changes expression of select gene products including the giant glycoprotein scavenger receptors cubulin and megalin, the structural microvillar protein villin, and classic shear stress response genes ICAM, VCAM and MnSOD. Using a putative endothelial cell shear stress response element binding site as a decoy, we demonstrate the role of this sequence in the regulation of selected genes in epithelial cells. However, many of the changes observed in the rotating wall vessel are independent of this response element. It remains to define other genetic response elements modulated during rotating wall vessel culture, including the role of hemodynamics characterized by 3-dimensionality, low shear and turbulence, and cospatial relation of dissimilar cell types. Received: 30 June 1998/Revised: 30 November 1998     

Core and Satellite Species in Degraded Habitats: an Analysis Using Malagasy Tree Communities

Core-satellite theory predicts that, via the “rescue effect”, widespread, abundant species should have reduced risk of local extinctions. We test this hypothesis in southeastern Malagasy littoral forest using data on distribution and abundance of trees and woody understory vegetation in tropical forest fragments along a disturbance gradient. We partition the mortality risk into two kinds of extinction factors, separately operating at demographic (local) and landscape (regional) scales, contrary to core-satellite predictions, for both trees and woody understory vegetation, that the relative number of core (abundant) species declined significantly with increasing disturbance. In the least-degraded forest fragments there was a strong mode of core species, while in the moderately- and severely-degraded fragments the species distributions were essentially log-normal, lacking a substantial core mode. While the rescue effect mitigates one kind of extinction risk, namely local environmental and demographic stochasticity, it may not counterbalance widespread pervasive sources of mortality. The amount of internal forest fragmentation appears to have a much greater effect on species richness and diversity than either fragment size or shape.     

Blood Glutathione as an Index of Radiation-Induced Oxidative Stress in Mice and Humans

The effect of x-rays on GSH and GSSG levels in blood was studied in mice and humans. An HPLC method that we recently developed was applied to accurately determine GSSG levels in blood. The glutathione redox status (GSH/GSSG) decreases after irradiation. This effect is mainly due to an increase in GSSG levels. Mice received single fraction radiotherapy, at total doses of 1.0 to 7.0 Gy. Changes in GSSG in mouse blood can be detected 10 min after irradiation and last for 6 h within a range of 2.0–7.0 Gy. The highest levels of GSSG (20.1 ± 2.9 ), a 4.7-fold increase as compared with controls) in mouse blood are found 2 h after radiation exposure (5 Gy). Breast and lung cancer patients received fractionated radiotherapy at total doses of 50.0 or 60.0 Gy, respectively. GSH/GSSG also decreases in humans in a dose–response fashion. Two reasons may explain the radiation-induced increase in blood GSSG: (a) the reaction of GSH with radiation-induced free radicals resulting in the formation of thyl radicals that react to produce GSSG; and (b) an increase of GSSG release from different organs (e.g., the liver) into the blood. Our results indicate that the glutathione redox ratio in blood can be used as an index of radiation-induced oxidative stress. © 1997 Elsevier Science Inc.     

Interpreting Diabetes Mellitus: Differences between Patient and Provider Models of Disease and their Implications for Clinical Practice

Current medical literature suggests that Type 2 diabetes mellitus can becontrolled by diet and hypoglycemic agents or diet and insulin therapy.Nevertheless, adhering to a low glucose dietary regimen remainsproblematic for a majority of patients, and management of the disease isan ongoing source of frustration for physicians and other providers.While calling for more research on the physician's experience oftreating chronic conditions like diabetes, the authors argue that muchof the current frustration stems from the different frames orexplanatory models that physicians and patients use to understand thedisease. By comparing physician narratives collected in several clinicalcontexts (e.g., medical lectures, precepting sessions, patient caresessions and personal interviews) with patient stories obtainedprimarily through narrative interviews, the authors highlight crucialdifferences in the way physicians and patients experience and thinkabout the disease. In particular, the authors highlight differencesbetween physicians and patients across five dimensions: etiology,symptoms/signs, factors which affect blood sugar, ideal blood sugar,and future prospects. In concluding, the authors sketch out elements ofa theory of clinical practice involving diabetes care. Data for thestudy was collected at two family practice training sites in Chicago.     

Tuberculosis in an Urban Area in China: Differences between Urban Migrants and Local Residents

Background

The increase in urban migrants is one of major challenges for tuberculosis control in China. The different characteristics of tuberculosis cases between urban migrants and local residents in China have not been investigated before.

Methodology/Principal Findings

We performed a retrospective study of all pulmonary tuberculosis patients reported in Songjiang district, Shanghai, to determine the demographic, clinical and microbiological characteristics of tuberculosis cases between urban migrants and local residents. We calculated the odds ratios (OR) and performed multivariate logistic regression to identify the characteristics that were independently associated with tuberculosis among urban migrants. A total of 1,348 pulmonary tuberculosis cases were reported during 2006–2008, among whom 440 (32.6%) were local residents and 908 (67.4%) were urban migrants. Urban migrant (38.9/100,000 population) had higher tuberculosis rates than local residents (27.8/100,000 population), and the rates among persons younger than age 35 years were 3 times higher among urban migrants than among local residents. Younger age (adjusted OR per additional year at risk = 0.92, 95% CI: 0.91–0.94, p<0.001), poor treatment outcome (adjusted OR = 4.12, 95% CI: 2.65–5.72, p<0.001), and lower frequency of any comorbidity at diagnosis (adjusted OR = 0.20, 95% CI: 0.13–0.26, p = 0.013) were significantly associated with tuberculosis patients among urban migrants. There were poor treatment outcomes among urban migrants, mainly from transfers to another jurisdiction (19.3% of all tuberculosis patients among urban migrants).

Conclusions/Significance

A considerable proportion of tuberculosis cases in Songjiang district, China, during 2006–2008 occurred among urban migrants. Our findings highlight the need to develop and implement specific tuberculosis control strategies for urban migrants, such as more exhaustive case finding, improved case management and follow-up, and use of directly observed therapy (DOT).