Laminar Blood Flow Research Articles

Pulsatile Non-Newtonian Laminar Blood Flows through Arterial Double Stenoses

The paper presents a numerical investigation of non-Newtonian modeling effects on unsteady periodic flows in a two-dimensional (2D) pipe with two idealized stenoses of 75% and 50% degrees, respectively. The governing Navier-Stokes equations have been modified using the Cartesian curvilinear coordinates to handle complex geometries. The investigation has been carried out to characterize four different non-Newtonian constitutive equations of blood, namely, the (i) Carreau, (ii) Cross, (iii) Modified Casson, and (iv) Quemada models. The Newtonian model has also been analyzed to study the physics of fluid and the results are compared with the non-Newtonian viscosity models. The numerical results are represented in terms of streamwise velocity, pressure distribution, and wall shear stress (WSS) as well as the vorticity, streamlines, and vector plots indicating recirculation zones at the poststenotic region. The results of this study demonstrate a lower risk of thrombogenesis at the downstream of stenoses and inadequate blood supply to different organs of human body in the Newtonian model compared to the non-Newtonian ones.

Multiple Atrial Communications presenting as Platypnea-Orthodeoxia Syndrome

We report a case of platypnea-orthodeoxia syndrome resulting from multiple inter-atrial communications with right-toleft shunting in a 73 year old woman. Our patient presented with progressive shortness of breath over the last eighteen months. She was on 10 liters of high flow oxygen at time of presentation to our hospital and was bed bound owing to severe dyspnea. Her history of chronic pulmonary emboli despite therapeutic coumadin levels and ulcerative colitis initially led to an exhaustive hepatopulmonary work-up. On clinical exam, she was noted to have normal oxygen saturation with lying down, but with sitting up or walking she developed significant hypoxia and respiratory distress. With no evidence of lung parenchymal or vascular diseases, right heart catheterization was performed and revealed normal right sided pressures. Intracardiac echocardiography confirmed a typical appearing patent foramen ovale (PFO) with atrial septal aneurysm and bidirectional shunting, and a small inferior secundum atrial septal defect (ASD). Although the ASD was congenital, aortic dilation with ageing could have altered the location of the atrial septum which facilitated laminar blood flow from the inferior vena cava to the left atrium. We proceeded to close both defects with an Amplatzer Cribiform Occluder. Her symptoms dramatically improved 48 hours following closure and she was ambulating on room air at time of discharge. One month follow-up was notable for no recurrence of symptoms. PFOs and small ASDs are generally innocuous but could cause right to left shunting even in the absence of elevated right sided pressures. Excluding other causes of platypnea-orthodeoxia, and closing the atrial communications can lead to resolution of symptoms. Key words: Multiple Atrial Communications, Platypnea-Orthodeoxia Syndrome.

Micro(RNA)managing Endothelial Regeneration

Systemic targeting of miR-126 production might be useful in treating atherosclerosis.

Cell Divisions Cause Long-Range Well-Ordered Vorticity Patterns in Endothelial Tissue

Endothelial cells line the blood vessels of the circulatory system and adhere tightly to their neighbors to prevent leakage, thus causing the cells to move within the endothelial monolayer i a highly collectively fashion. In healthy blood vessels with a laminar blood flow, the endothelial cell division rate is low, only sufficient to replace apoptotic cells. The division rate significantly increases during embryonic development and under halted or turbulent flow. Using PIV analysis we investigated the long-range dynamics induced by cell division in an endothelial monolayer under non-flow conditions, thus mimicking the conditions during vessel formation or around blood clots. A cell division locally injects energy into the system and strongly influences monolayer dynamics. We show that cell divisions induce long-range, well-ordered vortex patterns extending several cell diameters away from the division site. This is rather surprising considering the system's low Reynolds number. Our experimental results are reproduced by a hydrodynamic continuum model simulating division as a local pressure increase in a non-nematic, meso-scale turbulent state. The long-range physical communication may be crucial for embryonic development and for healing endothelial tissue around blood clots.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Laminar Blood Flow through a Model of Arterial Stenosis with Oscillating Wall

Laminar Blood Flow through a Model of Arterial Stenosis with Oscillating Wall

Usefulness of Doppler ultrasonography to assess digital vascular dynamics in horses with systemic inflammatory response syndrome or laminitis

To evaluate the usefulness of Doppler ultrasonography as a method to assess changes in digital vascular dynamics in horses with systemic inflammatory response syndrome (SIRS) or laminitis. Cross-sectional study. Animals-42 adult Andalusian horses. Group 1 included 9 healthy horses, group 2 included 19 horses with SIRS without (n = 9) or with (10) a palpable increase in digital pulse intensity, and group 3 included 14 horses with laminitis without (8) or with (6) radiographic evidence of rotation or distal displacement (sinking) of the third phalanx. Qualitative spectrum characteristics and quantitative Doppler measurements of the lateral palmar digital artery were obtained for horses in each group. 4 spectra, characterized by a positive systolic peak followed by several positive diastolic peaks, were observed in group 1 horses, group 2 horses, and group 3 horses that lacked radiographic changes. In the group 3 horses that had radiographic changes, laminar blood flow was detected. Diameter of the lateral palmar digital artery was significantly larger in the group 3 horses than in the group 2 horses; blood flow was significantly higher in the group 2 horses that had an increase in digital pulse intensity than in the group 2 horses without an increase in digital pulse intensity; velocity-time integral and acceleration time were significantly lower in group 3 horses, compared with group 2 horses. Results suggested that Doppler ultrasonography may be a useful complementary tool to detect digital blood flow changes of horses with SIRS, especially if they have a palpable increase in digital pulse intensity, or laminitis.

Viscous energy loss in the presence of abnormal aortic flow.

To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Four-dimensional flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n = 12, age = 37 ± 10 yr), patients with aortic dilation (n = 16, age = 52 ± 8 yr), and patients with aortic valve stenosis matched for age and aortic size (n = 14, age = 46 ± 15 yr), using a relationship between the three-dimensional velocity field and viscous energy dissipation. Viscous energy loss was elevated significantly in the thoracic aorta in patients with dilated aorta (3.6 ± 1.3 mW, P = 0.024) and patients with aortic stenosis (14.3 ± 8.2 mW, P < 0.001) compared with healthy volunteers (2.3 ± 0.9 mW). The same pattern of significant differences was seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2 ± 1.1 mW, P = 0.021) and patients with aortic stenosis (10.9 ± 6.8 mW, P < 0.001) were elevated compared with healthy volunteers (1.2 ± 0.6 mW). This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow.

Inhibitory effect of soluble RAGE in disturbed flow-induced atherogenesis

Soluble receptor for advanced glycation end products RAGE (sRAGE), a secretory form of RAGE, plays an important role in suppressing RAGE signals that induce pro-inflammatory gene activation in a range of inflammatory diseases, such as Alzheimer's disease, complications of diabetes mellitus and atherosclerosis. Recent studies have suggested that fluid shear stress generated by laminar blood flow protects blood vessels from atherosclerosis, whereas low and oscillatory shear stress (OSS) generated by disturbed blood flow causes atherosclerosis. Although RAGE levels are increased in atherosclerotic plaque, the regulatory mechanisms of sRAGE in the occurrence of atherosclerotic plaque induced by disturbed blood flow remain largely unknown. This study aimed to determine the effects of sRAGE as a competitive inhibitor of RAGE in atherogenesis induced by disturbed blood flow. To determine the role of sRAGE in atherosclerosis induced by disturbed blood flow, we used a mouse model of partial carotid artery ligation using ApoE(-/-) and C57BL/6 mice. Our results revealed that the expression of RAGE was significantly increased in the region of atherosclerotic plaque and that treatment with sRAGE attenuated the development of plaque formation. We found that the expression levels of RAGE and high mobility group box 1 (HMGB1), the agonistic ligand of RAGE, were significantly increased in human umbilical vein endothelial cells (HUVECs) under shear stress conditions induced by disturbed blood flow and suppressed following treatment with sRAGE. We further observed that treatment with sRAGE decreased the expression of vascular cell adhesion molecule‑1 (VCAM-1) and markedly attenuated monocyte-endothelial cell adhesion. Taken together, our results reveal that sRAGE exerts anti-atherogenic effects by blocking the activation of the RAGE signaling pathway induced by disturbed blood flow and may thus be a potential therapeutic target for the prevention of atherosclerosis.

PAR‐1 is a novel mechano‐sensor transducing laminar flow‐mediated endothelial signaling

Laminar blood flow acts mainly on vascular endothelial cells(ECs) which modulates atheroprotective functions. ECs express laminar flow‐mediating molecules of the mechano‐sensor including G proteins, integrin, and growth factor receptor. However, flow‐mediated signaling pathway of G protein and GPCR is not well established. Recent studies have indicated that PAR‐1 Known as GPCR which involves cytoprotective and anti‐inflammatory responses in endothelial cells. Here, we addressed whether the PAR‐1 is involved by laminar flow‐mediated atheroprotective signaling. In present study, depletion of PAR‐1 with siRNA against human PAR‐1 inhibited flow‐mediated KLF2‐and Nrf2‐dependent gene expression in ECs. In addition, confocal analysis showed that PAR‐1 was internalized into early endosome in response to laminar flow suggesting that PAR‐1 is activated by laminar blood flow. We identified HDAC5 as a downstream target molecule of PAR‐1. Furthermore depletion of PAR‐1 reversed the flow‐mediated anti‐inflammatory response for TNFa‐induced VCAM‐1 expression and monocyte adhesiveness. Taken together, these results provide that flow‐induced PAR‐1 activation exerts atheroprotective signaling pathway in ECs.

Total cavopulmonary connection in patients with apicocaval juxtaposition: optimal conduit route using preoperative angiogram and flow simulation†

Single ventricle with apicocaval juxtaposition (ACJ) is a rare, complex anomaly, in which the optimal position of the conduit for completion of total cavopulmonary connection (TCPC) is still controversial. The purpose of this study was to identify a preoperative method for optimal conduit position using the IVC anatomy and computational fluid dynamics (CFD). Twenty-four patients with ACJ (5.3 ± 5.7 years) who underwent TCPC were enrolled. A conduit was placed ipsilateral to the cardiac apex in each of 11 patients, of which 9 were intra-atrial and 2 extracardiac (group A) and, in a further 13 patients, extracardiac on the contralateral side (group B). As control, 10 patients with tricuspid atresia were also enrolled (group C). The location of the IVC in relation to the spine was evaluated from the frontal view of preoperative angiogram, using the following index: IVC-index = IVC width overlapping the vertebra/width of the vertebra × 100%. Energy loss was calculated by CFD simulation. IVC-index of group B was larger than groups A and C (45 ± 26 vs. 20 ± 21 and 28 ± 19%, P = 0.03). Postoperative catheterizations showed that, due to its curvature, conduit length in group B was significantly longer than the others (65 ± 12 vs. 36 ± 14 and 44 ± 10 mm, P < 0.001), although there was no statistical difference in central venous pressure or cardiac output. CFD studies revealed less energy loss in group A conduits compared with group B (1.6 ± 0.3 vs. 3.6 ± 0.6 mW, P = 0.05), although this did not appear to be clinically significant. Moreover, CFD simulation showed significant energy loss within the Fontan circulation when the conduit was either compressed or kinked: 4.9 and 18.2 mW respectively. In patients with ACJ, placement of a straighter and shorter conduit on the ventricular apical side provides better laminar blood flow with less energy loss. However, conduit compression and kinking are far more detrimental to the Fontan circulation. A preoperative IVC-index is pivotal for avoiding these factors and deciding the optimal conduit route.

Fluid-Structure Interaction Analysis of Pulsatile Blood Flow and Heat Transfer in Living Tissues During Thermal Therapy

The current numerical investigation tackles the fluid-structure interaction in a blood vessel subjected to a prescribed heating scheme on tumor tissues under thermal therapy. A pulsating incompressible laminar blood flow was employed to examine its impact on the flow and temperature distribution within the blood vessel. In addition, the arterial wall was modeled using the volume-averaged porous media theory. The motion of a continuous and deformable arterial wall can be described by a continuous displacement field resulting from blood pressure acting on the tissue. Moreover, discretization of the transport equations was achieved using a finite element scheme based on the Galerkin method of weighted residuals. The numerical results were validated by comparing them against documented studies in the literature. Three various heating schemes were considered: constant temperature, constant wall flux, and a step-wise heat flux. The first two uniform schemes were found to exhibit large temperature variation within the tumor, which might affect the surrounding healthy tissues. Meanwhile, larger vessels and flexible arterial wall models render higher variation of the temperature within the treated tumor, owing to the enhanced mixing in the vicinity of the bottom wall.

Differences in blood velocity simulated stented vessels between pulsed and laminar blood flow: An evaluation using numerical fluid dynamics (CFD)

Differences in blood velocity simulated stented vessels between pulsed and laminar blood flow: An evaluation using numerical fluid dynamics (CFD)

English

Introduction Anomalies and variations of the anterior communicating artery are common. Fenestration has been reported as the most common variation of this artery. Dolichoectasia of intracranial arteries is a rare arteriopathy characterised by elongation and widening of the arteries, mostly involving vertebral and basilar arteries. This report discusses large anterior communicating artery fenestration associated with posterior circulation anomalies. Case Report We report here a rare case of large anterior communicating artery fenestration associated with mild dolichoectasia of the basilar artery and marked dolichoectasia of the left posterior inferior cerebellar artery, forming a large vascular loop at the area of cisterna magna, as well as hypoplasia of the left anterior inferior cerebellar artery. The study discusses the details of this case. Conclusion Dolichoectasia of intracranial arteries is a rare arteriopathy characterised by elongation and widening of the arteries and disturbance of the laminar blood flow, mostly involving vertebral and basilar arteries.

The mechanism of the polymer-induced drag reduction in blood

Literature reports provide evidence that nanomolar concentrations of spaghetti-like, high molecular weight polymers decrease the hydrodynamic resistance of blood thereby improving impaired blood circulation. It has been suggested that the polymer-induced drag reduction is caused by the corralling of red blood cells (RBCs) among extended macromolecules aligned in the flow direction. This mechanism predicts that drag-reducing polymers must affect the conductivity of completely dispersed blood, time-dependent and steady state structural organization of aggregated RBCs at rest. However, experimental results obtained at the concentration of poly(ethylene oxide) (PEO, MW=4×106) of 35ppm show that neither the conductivity of completely dispersed blood, nor the kinetics of RBC aggregation occurring after the stoppage of flow, nor the structural organization of aggregated RBCs in the quiescent blood are affected by PEO. As these results are at odds with the “corralling” hypothesis, it is assumed that the effect of these polymers on the drag is associated with their interactions with local irregularities of disturbed laminar blood flow.

MicroRNAs Control Vascular Endothelial Growth Factor Signaling

Angiogenesis is a very tightly controlled process, in which endothelial cells need to migrate and proliferate toward ischemic tissue. A long-known factor that provides a gradient for endothelial cells to migrate toward is vascular endothelial growth factor (VEGF).1 Carefully titrated levels of VEGF are crucial for blood vessel development, because even the heterozygous deletion of VEGF is lethal in mice.2 In the past decades, it has become clear that VEGF signaling is very complex, with different VEGF isoforms and VEGF receptors that tightly control endothelial cell behavior. Interestingly, although VEGF receptor 2 (kinase insert domain receptor [KDR]) is one of the main proangiogenic VEGF receptors,3 binding of VEGF to VEGF receptor 1 (fms-related tyrosine kinase 1 [FLT1]) does not result in proangiogenic signaling, which raised the concept that FLT1 acts as a trap or decoy for VEGF. Thus, FLT1 can negatively regulate VEGF signaling, and this is of crucial importance, for instance, to keep the cornea avascular,4 but also aids in controlling the fine balance between proangiogenic and antiangiogenic factors. To make matters more complex, FLT1 mRNA is alternatively spliced, giving rise to a membrane-bound FLT1 and secreted soluble FLT1,5 but they both function as VEGF traps, preventing VEGF from activating KDR. In this issue of Circulation Research , Hassel et al6 …

Endothelial mechanosensors of shear stress as regulators of atherogenesis

Differences in local blood flow patterns along the endothelium may trigger abnormal vascular responses which can have profound pathophysiological consequences. While endothelial cells exposed to laminar blood flow (high shear stress) are protected from atherosclerosis formation, turbulent or disturbed blood flow, which occurs at bends and bifurcations of blood vessels, facilitates atherosclerosis formation. Here, we will highlight the endothelial cell mechanisms involved in detecting shear stress and their translation into downstream biochemical signals. Prior evidence supports a role for integrins as mechanotransducers in the endothelium by promoting phosphorylation of different targets through the activation of focal adhesion kinase. Our recent findings show that integrins contact integrin-linked kinase and regulate vasomotor responses by an endothelial nitric oxide synthase-dependent mechanism, which stabilizes the production of vasoactive factor nitric oxide. In addition, different structures of endothelial cells, mainly primary cilia, are investigated, as they can explain the differential responses to laminar versus disturbed flow. The discovery of a connection between endothelial cell structures such as cilia, integrin, extracellular matrix, and signaling events opens today a new chapter in our understanding of the molecular mechanisms regulating vascular responses to the changes in flow.

Dolichoektazja tętnic koła tętniczego Willisa i tętniak wrzecionowaty tętnicy podstawnej mózgu – opis przypadku i przegląd piśmiennictwa

Dolichoectasia of intracranial arteries is a rare arteriopathy characterized by elongation and widening of the arteries and disturbance of the laminar blood flow. It involves mostly vertebral and basilar arteries. In advanced cases, formation of a fusiform aneurysm is possible. A sixty-four-year-old female with hypertension was admitted to the hospital with severe non-systemic vertigo and dysarthria, which had lasted for a couple of weeks. Imaging of the brain revealed dolichoectasia of arteries of the circle of Willis coexisting with a fusiform aneurysm of the basilar artery. Intracranial arterial dolichoectasia may be asymptomatic for a long time. However, in many cases it leads to neurological symptoms associated with haemodynamic disturbance (due to unstable wall clots) and mass effect caused by the widened vessel.

Use of a Multilayered Stent for the Treatment of Hepatic Artery Pseudoaneurysm After Liver Transplantation

To the Editor: We would like to use this opportunity to share with the wider clinical community our experience in managing a hepatic artery pseudoaneurysm (HAP) of a 59-year-old man after liver transplant using a multilayered stent. HAP is a rare but well-recognised complication occurring after orthotopic liver transplantation (OLT). The reported incidence is 0.3% to 2.6% [1, 2]. The majority of cases of HAP occurring after OLT arise in the context of endovascular intervention or secondary to diathermy injury to the artery during surgery [3]. They have also been reported to complicate other hepato-pancreatico-biliary surgical procedures [4]. With time, the natural history of HAP is of enlargement and an associated risk of rupture, which can be fatal [5]. Patients most commonly present with intraperitoneal bleeding or gastrointestinal haemorrhage secondary to haemobilia; however, incidental and asymptomatic HAP may be recognised [6]. Established management options include surgical ligation and endovascular coil embolisation; however, both of these methods are associated with a significant risk of hepatic ischaemia, which often requires retransplantation [5]. Coronary artery stent-grafts have also been used to treat HAP, often after failure of coil embolisation [7]. The introduction of the Multilayer Aneurysm Repair System (MARS) stent (Cardiatis SA, Belgium) is a recent development in endovascular aneurysm repair. This is an uncovered stent comprised of three-dimensional braided tubing that decreases blood flow velocity in the aneurysmal sac whilst improving laminar blood flow in the main artery and surrounding arterial tributaries [8]. Its use for the treatment of HAP occurring after OLT has not previously been reported. Our case involves a 59 year-old man who underwent OLT for alcoholic cirrhosis in January 2011. The patient’s main indication for OLT was recurrent ascites. A transjugular intrahepatic portosystemic shunt was inserted in November 2010 before emergency surgical repair of a ruptured umbilical hernia. He was transplanted in early January 2011. He received a whole liver from a 74-year-old brainstem-dead donor who was involved in a road-traffic accident. His hepatectomy was performed whilst he was on veno-venous bypass and was uncomplicated. The implantation included a cavocavostomy, end-to-end pulmonary vein anastomosis using 5.0 Prolene (Ethicon, UK) suture material, end-to-end arterial anastomosis to the common hepatic artery using 6.0 Prolene (Ethicon, UK) suture material, and duct-to-duct biliary anastomosis using 5.0 polydioxanone (Ethicon, UK) suture material. The cold ischaemic time was 12 h and 40 min. During surgery, he received 4 U of blood, 1 pool of platelets, and 6 U of fresh frozen plasma. His postoperative recovery was complicated by mild acute cellular rejection on day 10, which required augmentation with intravenous methylprednisolone. He was discharged home on day 16. His immunosuppression medication included tacrolimus, azathioprine, and prednisolone. Because he was a cytomegalovirus mismatch, vanganciclovir was given for 100 days. At 3 months after OLT, the patient was admitted to our hospital for investigation of graft dysfunction. Liver histology showed evidence of perivenular haemorrhage and A. M. Elsharkawy (&) G. Sen M. Hudson S. Masson D. M. Manas Liver Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne NE7 7DN, UK e-mail: ahmede@doctors.org.uk

Unrepaired Tetralogy of Fallot with Major Aortopulmonary Collateral Arteries in an Adult Patient

Tetralogy of Fallot is characterized by a ventricular septal defect, a large, overriding aorta, subpulmonic stenosis, and right ventricular hypertrophy. These lesions can be associated with abnormal development of the pulmonary vasculature. This can include peripheral pulmonic stenosis, discontinuous pulmonary arteries, anomalous pulmonary venous return, and the development of aortopulmonary collateral vessels. Aortopulmonary collateral vessels develop to supply underperfused areas of the pulmonary bed and pose a unique and challenging problem at the time of surgical repair, which involves closure of the ventricular septal defect, relief of right ventricular outflow tract obstruction, maintenance of pulmonary valve competency when possible, and establishment of laminar pulmonary blood flow to all segments of the pulmonary bed. We describe a 36-year-old man with unrepaired tetralogy of Fallot with distinctive aortopulmonary collaterals, who underwent complete surgical repair with good outcome. Two-dimensional echocardiogram, cardiac magnetic resonance imaging, and cardiac catheterization each provided vital details allowing a stepwise approach to defining his unique anatomy for surgical correction.

Surgical Strategy for Aortic Coarctation Repair Resulting in Physiologic Arm and Leg Blood Pressures

The goal of aortic coarctation repair is laminar aortic blood flow resulting in a negative or absent arm:leg blood pressure (BP) gradient. Despite satisfactory relief of coarctation, associated arch hypoplasia can result in residual obstruction and postoperative upper body hypertension. We devised a surgical strategy to create a tension-free anastomosis with a diameter as large as both the adjacent proximal and distal aorta using a radically extended end-to-end anastomosis via sternotomy and/or thoracotomy. Sternotomy is chosen when there is significant transverse arch hypoplasia defined as a distal transverse arch ≤ diameter of the left carotid artery, presence of a common brachiocephalic trunk, or coexisting intracardiac lesion requiring repair. Thoracotomy is used in all other cases. From 2000 to 2008, 95 consecutive patients were repaired using this approach, 35 with sternotomy and 60 with thoracotomy. At a mean follow-up of 50 ± 23 months, mean systolic BP was 94 ± 10 mm Hg, and 84% of patients had no residual arm:leg BP gradient. Mean arm:leg BP gradient was not statistically different between groups (-8.5 ± 15 sternotomy and -7.0 ± 10 mm Hg thoracotomy, P= .7). With Doppler echocardiography, 96% of patients demonstrated normal early diastolic reversal of blood flow in the descending thoracic aorta. For aortic coarctation repair in infancy, a strategy designed to directly address aortic arch hypoplasia results in excellent intermediate-term results with normal BP, physiologic arm:leg BP relationship, and near normal descending aortic blood flow velocities by Doppler.