Is smooth muscle growth in primate arteries regulated by endothelial nitric oxide synthase?

PURPOSE: We investigated whether control of constitutive endothelial cell nitric oxide synthase (cNOS) and nitric oxide (NO) by changes in shear stress might be important for the regulation of smooth muscle cell (SMC) growth and vascular diameter. METHODS: Bilateral femoral arteriovenous fistulas were placed in baboons to increase the blood flow in the external iliac arteries. At 2 months, the fistula was ligated on one side to restore normal flow (flow switch). RESULTS: In response to flow switch and a decrease in shear stress, iliac artery lumenal area decreased and SMC proliferation was induced. A decline in NO production, cNOS messenger RNA (mRNA), and protein were associated with these biological effects. In a subset of animals with iliac arteries under high flow, infusion of N(omega)-nitro-L-arginine, an inhibitor of cNOS, did not induce proliferation. CONCLUSION: Shear stress can regulate cNOS, vasoconstriction, and SMC proliferation. A decrease in nitric oxide may be necessary, but is not sufficient to induce SMC proliferation in response to a decrease in blood flow.     

Alterations in pulmonary artery flow patterns and shear stress determined with three-dimensional phase-contrast magnetic resonance imaging in Fontan patients

OBJECTIVE: This study compares in vivo pulmonary blood flow patterns and shear stresses in patients with either the direct atrium-pulmonary artery connection or the bicaval tunnel connection of the Fontan procedure to those in normal volunteers. Comparisons were made with the use of three-dimensional phase contrast magnetic resonance imaging. METHODS: Three-dimensional velocities, flows, and pulmonary artery cross-sectional areas were measured in both pulmonary arteries of each subject. Axial, circumferential, and radial shear stresses were calculated with the use of velocities and estimates of viscosity. RESULTS: The axial velocities were not significantly different between subject groups. However, the flows and cross-sectional areas were higher in the normal group than in the two patient groups in both pulmonary arteries. The group with the bicaval connection had circular swirling in the cross section of both pulmonary arteries, causing higher shear stresses than in the controls. The disorder caused by the connection of the atrium to the pulmonary artery caused an increase in some shear stresses over the controls, but not higher than those found in the group having a bicaval tunnel. CONCLUSIONS: We found that pulmonary flow was equally reduced compared with normal flow in both patient groups. This reduction in flow can be attributed in part to the reduced size of the pulmonary arteries in both patient groups without change in axial velocity. We also found higher shear stress acting on the wall of the vessels in the patients having a bicaval tunnel, which may alter endothelial function and affect the longevity of the repair.     

Computational analysis of flow in a curved tube model of the coronary arteries: effects of time-varying curvature

The flow through a curved tube whose radius of curvature varies with time was studied in order to better understand flow patterns in coronary arteries. A computational flow model was constructed using commercially available software. The artery model featured a uniform circular cross section, and the curvature was assumed to be constant along the tube, and in one plane. The computational model was verified with the use of a dynamically similar in vitro apparatus. A steady uniform velocity was prescribed at the entrance at a Reynolds number of 300. Two sets of results were obtained: one in which the curvature was held constant at the mean, maximum and minimum radii of curvature (quasistatic), and another in which the curvature was varied sinusoidally in time at a frequency of I Hz (dynamic). The results of the dynamic analysis showed that the wall shear rates varied as much as 52% of the static mean wall shear rate within a region of 10 tube diameters from the inlet. The results of the dynamic analysis were within 6% of the quasistatic predictions. Realistic modeling of the deforming geometry is important in determining which locations in the coronary arteries are subjected to low and oscillating wall shear stresses, flow patterns that have been associated with atherogenesis.     

Pharmacodynamics of intracavernously injected drugs and cavernous wall resistance

The volumetric flow rates, mean and pulsatile, in the aorta and its major branches were measured in nonfed, anesthetized rabbits, using a transit time Doppler ultrasonic flowmeter. Anesthesia was maintained with isoflurane, and a vasodilator was applied topically during the measurements to avoid introducing additional flow resistance due to vasoconstriction. The cranial mesenteric and celiac arteries received the bulk of the aortic flow, (mean +/- SD) 29.5 +/- 6.6% and 23.3 +/- 5.8%, respectively, for mean flow. The brachiocephalic artery received as much as 14.7 +/- 3.2%, while each of the other branches received a considerably smaller fraction: 7.1 +/- 2.5% for the left subclavian artery, 6.2 +/- 2.6% and 5.1 +/- 2.2%, respectively, for the right and left renal arteries, and 6.0 +/- 2.5% for each of the two iliac arteries. Flow divisions were nearly the same in paired vessels. Peak pulsatile flow divisions were similar to their steady flow counterparts in the brachiocephalic, left subclavian, celiac, and cranial mesenteric arteries, but were smaller in the renal and iliac arteries, although the difference was not statistically significant. Reverse flow from one or more of the branches back into the aorta occurred in diastole in seven of eight rabbits studied.     

Contraction and endothelium dependent relaxation via alpha adrenoceptors are variable in various pig arteries

OBJECTIVE: The aim was to examine differences in the vascular response to alpha adrenoceptor stimulation on both smooth muscle and endothelium among large arteries perfusing various organs. METHODS: In ring preparations of coronary, carotid, iliac, mesenteric, and renal arteries from pigs (n = 24), the magnitudes of contraction to noradrenaline (with beta blocker), with or without endothelium, and endothelium dependent relaxation to noradrenaline (with alpha 1 and beta blocker) were compared in vitro. RESULTS: In both endothelium-intact and denuded groups, the contractions to noradrenaline were significantly smaller in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. The presence of endothelium significantly suppressed the contractions in coronary and carotid arteries, but did not affect the contractions in iliac, mesenteric, and renal arteries. The endothelium dependent relaxations to noradrenaline, which were abolished by LNMMA, were more prominent in coronary and carotid arteries than in iliac, mesenteric, and renal arteries. CONCLUSIONS: The contractions via alpha adrenoceptors were small, and endothelium dependent relaxations via alpha 2 adrenoceptors were large, in the coronary and carotid arteries, which perfuse the vital organs (heart and brain), as compared with those in iliac, mesenteric, and renal arteries. These results suggest that in the state of activation of the sympathetic nervous system, arterial tone in response to alpha adrenoceptor stimulation may be regulated not only by alpha adrenoceptors on vascular smooth muscle but also by those on endothelium, through release of endothelium derived relaxing factor (EDRF) via alpha 2 adrenoceptors.     

Three-Dimensional Numerical Simulation of Compound Channel Flows

A three-dimensional numerical study is presented for the calculation of turbulent flow in compound channels. The flow simulations are performed by solving the three-dimensional Reynolds-averaged continuity and Navier–Stokes equations with the k?ε turbulence model for steady-state flow. The flow equations are solved numerically with a general-purpose finite-volume code. The results are compared with the experimental data obtained from the UK Flood Channel Facility. The simulated distributions of primary velocity, bed shear stress, turbulent kinetic energy, and Reynolds stresses are used to investigate the accuracy of the model prediction. The results show that, using an estimated roughness height, the primary velocity distributions and the bed shear stress are predicted reasonably well for inbank flows in channels of high aspect ratio (width/depth ≥ 10) and for high overbank flows with values of the relative flow depth greater than 0.25.     

Effect of gadolinium on phase-contrast MR angiography of the renal arteries

OBJECTIVE: Our aim was to evaluate the effect of gadolinium chelates on image quality in phase-contrast MR angiography of renal arteries in patients suspected of having renal artery stenosis. MATERIALS AND METHODS: In 24 patients, axial three-dimensional phase-contrast MR angiography of the renal arteries was obtained on a 1.5-T MR imaging system before and after administration of gadolinium contrast agent. The improvement in distal renal artery signal-to-noise ratio after enhancement was measured and correlated with patient age, serum creatinine level, clinical estimation of renal artery flow, and the imaging parameter flip angle. RESULTS: On average, the distal renal artery signal-to-noise ratio increased 2.2-fold after gadolinium administration (p < .001). The increase was greatest in patients more than 60 years old (3.1-fold; p < .001) and in patients with serum creatinine levels greater than 3.0 mg/dl (4.3-fold; p < .01). After enhancement, we found an apparent increase in renal artery diameter (3.5 +/- 1.1 mm before enhancement versus 4.8 +/- 1.4 mm after enhancement [mean +/- SD; p < .001]). We believe this increase reflects improved visualization of slow blood flow along the artery wall. Although the visualization of renal arteries was better in most patients after enhancement, two patients had poorer image quality after enhancement because of increased venous signal obscuring the arteries. CONCLUSION: Gadolinium administration significantly increases distal renal artery signal-to-noise ratio on three-dimensional phase-contrast MR angiography in most patients. The signal-to-noise ratio improvement is greatest in older patients and in patients with impaired renal function. However, in some cases, increased venous signal may obscure arteries.     

Role of EDRF in the regulation of shear rate in large coronary arteries in conscious dogs

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 +/- 1% in external diameter and by 11 +/- 4% in internal diameter) and for 30 s occlusions before NLA (by 5 +/- 1% in external diameter and by 14 +/- 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 mumol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.     

Nonlinear Mixing Length Model for Prediction of Secondary Currents in Uniform Channel Flows

A nonlinear turbulence model for numerical solution of uniform channel flow is presented. Turbulent stresses are evaluated from a nonlinear mixing length model that relates turbulent stresses to quadratic products of the mean rate of strain and the mean vorticity. The definition of the mixing length, based on a three-dimensional integral measure of boundary proximity, eliminates the need for solution of additional transport equations for the turbulence quantities. Experimental data from the literature for closed and open-channel flows are utilized to validate the model. The model produced the secondary flow vortices successfully. Velocity field and wall shear stresses affected by secondary flow vortices are accurately computed. Bulging of velocity contour lines toward the corners and dipping phenomena of maximum velocity are successfully simulated.     

Immunocytochemical localization of the alpha-1B adrenergic receptor and the contribution of this and the other subtypes to vascular smooth muscle contraction: analysis with selective ligands and antisense oligonucleotides

The contribution of the alpha-1B adrenergic receptor (AR) to vascular smooth muscle contraction has been assessed using a combination of immunological, molecular biological and pharmacological approaches. A subtype-selective antibody detected alpha-1B immunoreactivity in the medial layer of the aorta, caudal, femoral, iliac, mesenteric resistance, renal and superior mesenteric arteries. Receptor protection assays and antisense oligonucleotides were used to assess the contribution of the alpha-1B AR to contraction. The alpha-1B AR was implicated in mediating the phenylephrine-induced contraction of the mesenteric resistance artery. The alpha-1D AR was implicated in mediating the contraction of the aorta, femoral, iliac and superior mesenteric arteries. Similarly, the alpha-1A AR was implicated in mediating contraction of the caudal and renal arteries. In vivo application of antisense oligonucleotides targeted to the translational start site of the alpha-1B AR had no effect on the phenylephrine-induced contraction of the femoral or renal arteries. In contrast, antisense oligonucleotides directed against the alpha-1D AR significantly inhibited the phenylephrine response in the femoral artery but had no effect on the renal artery. Application of alpha-1A AR antisense oligonucleotides inhibited the contraction of the renal artery without effect on the femoral artery. These data show that (1) alpha-1B AR immunoreactivity is widely distributed in the same peripheral arteries in which previous studies detected its mRNA, and (2) despite this distribution, receptor protection and antisense oligonucleotide studies indicate that the alpha-1B AR mediates the contraction of only the mesenteric resistance artery.     

Inverse effect of chronically elevated blood flow on atherogenesis in miniature swine

The effect of chronically elevated blood flow on the development of atherosclerosis in miniature swine was studied. Fistulas connecting the right external iliac artery and vein were surgically created in four swine, while three were not fistulated. Pulsed Doppler velocity detection cuffs placed around the abdominal aorta and both iliac arteries of all pigs permitted chronic measurements of blood velocity, blood velocity distributions, and blood flow. All swine were fed an atherogenic diet consisting of 20% beef tallow, 3% cholesterol, and 5% cholic acid for 6 months. This diet elevated the serum cholesterol to values exceeding 500 mg/100 ml. Creation of the arteriovenous fistula (AVF) markedly elevated blood velocity and flow in the abdominal aorta and in the shunted iliac artery. In the shunted animals the aortic blood flow was 42.1 +/- 2.0 ml/sec compared with 17.3 +/- 1.4 ml/sec in the unshunted swine. The velocity distribution pattern across the vessel was also indicative of an elevated wall shear stress. After 6 months, the animals were killed and the arterial vessels examined macroscopically and microscopically for the presence of atherosclerotic lesions. In the shunted pigs, 17 +/- 15% of the lumenal surface was occupied by sudanophilic lesions, whereas 80 +/- 8% of the surface was covered by lesions in the unshunted (control) pigs. From these studies, it is apparent that mechanical factors related to blood flow rates can influence the development of atherosclerotic lesions in swine.     

Electron-beam CT-angiography in abdominal aortic aneurysms. Initial results

PURPOSE: To evaluate the suitability of ultrafast electron-beam tomography (EBT) for the investigation of abdominal aortic aneurysms using CTA. METHODS: Thirty-one patients with suspected abdominal aortic aneurysm were investigated with EBT using an Evolution XP scanner (Siemens, Erlangen) with the newest software version 12.34 with continuous volume scanning of 140 images in 17 s. Collimation was 3 mm, table increment 4 mm with overlapping image reconstruction every 2 mm, exposure time 200 ms (124 mAs), resulting in a scan-range of 28 cm. A quantity of 80 ml contrast material was administered (flow 4 ml/s). Visualization of the abdominal aorta and its branches was performed with MIPs and shaded surface display. Evaluation of image quality was based on a four-step classification scale (1 = good, 4 = insufficient) for the demonstration of the abdominal aorta and the visceral, renal and iliac arteries. RESULTS: All EBT examinations demonstrated high and homogeneous density values along the whole vessel course with a mean density value of 258.7 +/- 47.3 HU for the abdominal aorta and the iliac arteries. Quality evaluation for the vessel demonstration showed mean values between 1.22 and 1.57 for the abdominal aorta and the visceral, renal and iliac arteries. CONCLUSIONS: EBT with 140 slices and slice reconstruction every 2 mm offers a high z-axis resolution resulting in high-quality CT angiographies of the whole abdominal aorta and its branches.     

Shear Stress Distribution in Partially Filled Pipes

Boundary shear stresses have been calculated for circular pipes with a flat sediment bed using computational fluid dynamics (CFD). First of all, CFD simulations were carried out for rectangular channels in order to check the software package for its ability to reproduce experimental (literature) results. The influence of the applied turbulence model (isotropic or anisotropic) was also studied for rectangular channels. The simulations for circular pipes, using an isotropic turbulence model, were done for different filling ratios, mean flow velocities, and roughness heights. For validation, the numerical results were compared with former experimental work. With the help of the detailed shear stress distribution, sediment transport can be calculated more accurately than using the global shear stress, as is traditionally done. This method was applied to a simple flume experiment, subjected to a triangular inflow hydrograph, and the comparison with the traditional approach was made.     

Dynamics of Air Flow in Sewer Conduit Headspace

Pressurization in sanitary sewer conduit atmosphere is modeled using computational fluid dynamics techniques. The modeling approach considers both turbulent and laminar flow regimes. The turbulent model takes into consideration the turbulence-driven secondary currents associated with the sewer headspace and hence the Reynolds equations governing the air flow field are closed with an anisotropic closure model which comprises the use of the eddy viscosity concept for the turbulent shear stresses and semiempirical relations for the turbulent normal stresses. The resulting formulations are numerically integrated. The turbulent model outputs are verified with experimental data reported in the literature. Satisfactory agreement is obtained between numerical simulations and experimental data. Mathematical formulas and curves as functions of longitudinal pressure gradient, wastewater velocity, and sewer headspace geometry are developed for the cross-sectional average streamwise velocity.     

Brief report: successful extension of the transplant renal vein with a synthetic vascular graft

Unexpected intraoperative vascular complications in the graft of the recipient during organ transplantation can be most vexing and require immediate attention and careful management so as not to impair the integrity and fate of the graft. We were confronted with a diabetic recipient with total fibrosis of the left iliac vein, patent inferior vena cava, totally and circumferentially calcified aorta and left iliac artery with the exception of a small area in the distal external iliac artery. The problem was solved by anastomosing the artery low onto the external iliac, and by interposing a venous polytetrafluoroethylene vascular graft between the renal vein and the inferior vena cava. The kidney function was excellent for 2 years but the patient succumbed to unrelated liver complications. A second patient with a renal vein PTFE graft has had normal graft function for 10 years. Probably because of the high blood flow through the kidney, venous synthetic grafts can be successfully used to correct venous problems during kidney transplantation.     

Flow visualization and 1- and 3-D laser-Doppler-anemometer measurements in models of human carotid arteries

Pulsatile flow, wall distensibility, non-Newtonian flow characteristics of blood in flow separation regions, and high/low blood pressure were studied in elastic silicon rubber models having a compliance similar to human vessels and the same surface structure as the biological intima models of (1) a healthy carotid artery model, (2) a 90% stenosis in the ICA, and (3) 80% stenosis in both the internal and external carotid arteries. Flow was visualized for steady flow and pulsatile studies to localize flow separation regions and reattachment points. Local velocity was measured with a 1-, 2-, or 3-D laser-Doppler-anemometer (LDA). Flow in the unstenosed model was Re = 250. In the stenosed models, the Re number decreased to Re = 180 and 213 under the same experimental conditions. High velocity fluctuations with vortices were found in the stenosed models. The jet flow in the stenosis increased up to 4 m/s. With an increasing bifurcation angle, the separation regions in the ECA and ICA increased. Increased flow (Re = 350) led to an increase in flow separation and high velocity shear gradients. The highest shear stresses were nearly 20 times higher than normal. The 90% stenosis created high velocity shear gradients and velocity fluctuations. Downstream of the stenoses, eddies were found over the whole cross-section. In the healthy model a slight flow separation region was observed in the ICA at the branching cross-section whereas in the stenosed models, the flow separation regions extended far into the ICA. We conclude that a detailed understanding of flow is necessary before vascular surgery is performed especially before artificial grafts or patches are implanted.     

Quantification of the passive mechanical properties of the resting platelet

Sudden coronary artery occlusion is one of the leading causes of death. Several in vitro models have been used to study the relationship between hemodynamic forces and platelet function. However, very few in vivo studies exist that fully explore this relationship due to the lack of rheologic data for the platelet. For this purpose, micropipette aspiration techniques were used in the present study to determine the mechanical properties of platelets. The data were analyzed by two mathematical models: (1) an erythrocyte-type membrane model which yielded a platelet shear modulus of 0.03+/-0.01 dyn cm[-1] (mean+/-SD) and a viscous modulus of 0.12+/-0.04 dyn s cm[-1]. (2) An endothelial-type cell model which approximated the platelet Young's modulus to be 1.7+/-0.6 x 10(3) dyn cm(-2) with a viscous modulus of 1.0+/-0.5 x 10(4) dyn s cm(-2). The endothelial-type cell model more accurately describes the mechanics occurring at the micropipette tip and permits more appropriate assumptions to be made in quantifying the rheologic properties of a platelet. Results from this study can be integrated into numerical models of blood flow in stenosed coronary arteries to elucidate the impact of local hemodynamics on platelets and thrombus formation in coronary artery disease.     

Congenital malformations in infants of 517 pregestational diabetic mothers

PURPOSE: To explore a method of combined endovascular/conventional treatment of abdominal aortic aneurysm (AAA), in which the iliac arteries are reconstructed by conventional surgical techniques to provide the anatomic substrate for subsequent endovascular repair of the aortic aneurysm. METHOD: A 77-year-old patient with severe cardiac disease was found to have a 6.5-cm AAA, bilateral common iliac artery (CIA) aneurysms, and diffusely narrowed, tortuous external iliac arteries. The left internal iliac artery was occluded. At operation, the right CIA was exposed through a transverse retroperitoneal incision under epidural anesthesia. An iliobifemoral bypass was constructed using a preformed bifurcated graft. A stent-graft was delivered through the right limb of the bifurcated iliobifemoral graft. The proximal end of the stent-graft was implanted in the neck of the aneurysm, and the distal end was deployed in the common trunk of the iliobifemoral graft, thereby excluding the AAA and both native iliac arteries from prograde arterial flow. RESULTS: Completion angiography and follow-up contrast computed tomography showed the aneurysm to be excluded from the circulation. The patient was not intubated, was never hemodynamically unstable, and had aortic blood flow interrupted for no more than 20 seconds. In addition, he was able to resume his usual diet on the first postoperative day. He continues to be well and without evidence of endoleak at 6-month follow-up. CONCLUSIONS: This case demonstrates that iliac artery stenosis, tortuosity, and aneurysmal dilatation are not impediments to endovascular AAA exclusion. Any necessary surgical modifications of pelvic arterial anatomy can be performed before stent-graft insertion to minimize aortic occlusion time.     

Changes in pulmonary physiology after lung volume reduction surgery in a rabbit model of emphysema

BACKGROUND: We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model. METHODS: Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing. RESULTS: Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups. CONCLUSIONS: MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.     

Experimental Study of Interfacial Shear Stresses in FRP-Strengthened RC Beams

This paper presents the results of an experimental study on the distribution of shear stresses along the interface between concrete and the carbon fiber-reinforced polymer (FRP) in 29 plate-strengthened beams, where the primary test variables are: Clear cover, plate length, plate thickness (area), and compressive strength of concrete. FRP strain measurement was accomplished using either the photographic technique of digital image correlation or a series of electrical-resistance strain gages, both providing similar results. The distribution of shear stresses is found to be smoother than predicted by several analytical expressions available in the literature. Another substantial observation is the existence of a second region of peak stress, occurring near the center of the shear span in all of the beams with longer plate lengths, which the authors believe is associated with the singular application of shear corresponding to the point load, as well as the transition from elastic to plastic behavior occurring in the rebar. Because the overall nature of the stress distribution is sufficiently smooth, it is very reasonable to approximate it as a constant stress.