Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution

Mechanisms of in-stent restenosis are not fully understood. Shear stress is known to play a role in plaque and thrombus formation and is sensitive to changes in regional vessel geometry. Hence, we evaluated the regional changes in 3-D geometry and shear stress induced by stent placement in coronary arteries of pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D geometry was used to calculate locally the curvature, while the shear stress distribution was obtained by computational fluid dynamics. Local changes in shear stress were obtained at the entrance and exit of the stent for baseline (0. 65+/-0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent implantation, the curvature increased by 121% at the entrance and by 100% at the exit of the stent, resulting in local changes in shear stress. In general, at the entrance of the stent local maxima in shear stress were generated, while at the exit both local maxima and minima in shear stress were observed (p<0.05). Additionally, the shear stress at the entrance and exit of the stent were correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation changes 3-D vessel geometry in such a way that regions with decreased and increased shear stress occur close to the stent edges. These changes might be related to the asymmetric patterns of in-stent restenosis.     

Developing pulsatile flow in a deployed coronary stent

A major consequence of stent implantation is restenosis that occurs due to neointimal formation. This patho-physiologic process of tissue growth may not be completely eliminated. Recent evidence suggests that there are several factors such as geometry and size of vessel, and stent design that alter hemodynamic parameters, including local wall shear stress distributions, all of which influence the restenosis process. The present three-dimensional analysis of developing pulsatile flow in a deployed coronary stent quantifies hemodynamic parameters and illustrates the changes in local wall shear stress distributions and their impact on restenosis. The present model evaluates the effect of entrance flow, where the stent is placed at the entrance region of a branched coronary artery. Stent geometry showed a complex three-dimensional variation of wall shear stress distributions within the stented region. Higher order of magnitude of wall shear stress of 530 dyn/cm2 is observed on the surface of cross-link intersections at the entrance of the stent. A low positive wall shear stress of 10 dyn/cm2 and a negative wall shear stress of -10 dyn/cm2 are seen at the immediate upstream and downstream regions of strut intersections, respectively. Modified oscillatory shear index is calculated which showed persistent recirculation at the downstream region of each strut intersection. The portions of the vessel where there is low and negative wall shear stress may represent locations of thrombus formation and platelet accumulation. The present results indicate that the immediate downstream regions of strut intersections are areas highly susceptible to restenosis, whereas a high shear stress at the strut intersection may cause platelet activation and free emboli formation.     

Smaller, stiffer coronary bypass can moderate or reverse the adverse effects of wave reflections.

The question of whether the mechanical stiffness of a coronary bypass or that of a diseased coronary artery can have a significant effect on the hemodynamics in these vessels is addressed analytically, with emphasis on the effects of wave reflections. The analysis is based on a model of the vessels involved, and the results show the essential hemodynamic effects in each vessel. It is found that in the absence of a bypass graft, wave reflections resulting from a narrowing and stiffening of a diseased coronary artery have the effect of actually aiding the flow in the diseased vessel. In the presence of a bypass graft, however, the effects of wave reflections are reversed and become adverse to flow in both the bypass graft and the diseased coronary artery. A stiffer bypass moderates these effects and is therefore preferable to a more elastic bypass. The adverse effects also depend critically on the relative diameter of the bypass. Here the results indicate that a bypass of smaller diameter than that of the native coronary artery can moderate and even reverse the adverse effects of wave reflections resulting from the presence of the bypass.     

Computational haemodynamics in two idealised cerebral wide-necked aneurysms after stent placement

Endovascular stents are being commonly used to treat cerebral wide-necked aneurysms recently. The effect of a stent placed in the parent artery is not only to protect the parent artery from occlusion, due to extension of coils and thrombosis, but also to act as flow diverter to vary the haemodynamics in the aneurysm. In this article, two idealised cerebral wide-necked aneurysms were created, one was sidewall aneurysm with curved parent vessel and the other was terminal aneurysm with the bifurcated parent vessel. The plexiglass models of the two aneurysms were ‘treated’ with commercial porous intravascular stents. The stented physical models were scanned by Micro-CT and the numerical models of the two idealised cerebral wide-necked aneurysms after stent placement were constructed from the scanned image files. The pulsatile flow of non-Newtonian fluid inside the models was simulated by using computational fluid dynamics package. From the simulated flow dynamics, various haemodynamic characteristics such as velocity contours, wall shear stress and oscillatory shear index (OSI) were computed. The velocity of the jet entering the sacs reduced after stent was deployed across the necks of both sidewall and terminal aneurysms; the wall shear stress on the distal neck of sidewall aneurysm reduced, the wall shear stress on the dome of the terminal aneurysm increased and the OSI on the dome of the terminal aneurysm reduced. Therefore, stent placement not only promotes thrombus formation in both aneurysm models but also reduces the regrowth risk of the sidewall aneurysm and the rupture risk of the terminal aneurysm.     

Haemodynamic impact of stent–vessel (mal)apposition following carotid artery stenting: mind the gaps!

Carotid artery stenting (CAS) has emerged as a minimally invasive alternative to endarterectomy but its use in clinical treatment is limited due to the post-stenting complications. Haemodynamic actors, related to blood flow in the stented vessel, have been suggested to play a role in the endothelium response to stenting, including adverse reactions such as in-stent restenosis and late thrombosis. Accessing the flow-related shear forces acting on the endothelium in vivo requires space and time resolutions which are currently not achievable with non-invasive clinical imaging techniques but can be obtained from image-based computational analysis. In this study, we present a framework for accurate determination of the wall shear stress (WSS) in a mildly stenosed carotid artery after the implantation of a stent, resembling the commercially available Acculink (Abbott Laboratories, Abbott Park, Illinois, USA). Starting from angiographic CT images of the vessel lumen and a micro-CT scan of the stent, a finite element analysis is carried out in order to deploy the stent in the vessel, reproducing CAS in silico. Then, based on the post-stenting anatomy, the vessel is perfused using a set of boundary conditions: total pressure is applied at the inlet, and impedances that are assumed to be insensitive to the presence of the stent are imposed at the outlets. Evaluation of the CAS outcome from a geometrical and haemodynamic perspective shows the presence of atheroprone regions (low time-average WSS, high relative residence time) colocalised with stent malapposition and stent strut interconnections. Stent struts remain unapposed in the ostium of the external carotid artery disturbing the flow and generating abnormal shear forces, which could trigger thromboembolic events.     

Conductance catheter measurements of lumen area of stenotic coronary arteries: theory and experiment

An injection of saline solution is required for the measurement of vessel lumen area using a conductance catheter. The injection of room temperature saline to displace blood in a vessel inevitably involves mass and heat transport and electric field conductance. The objective of the present study is to understand the accuracy of conductance method based on the phenomena associated with the saline injection into a stenotic blood vessel. Computational fluid dynamics were performed to simulate flow and its relation to transport and electric field in a stenotic artery for two different sized conductance catheters (0.9 and 0.35 mm diameter) over a range of occlusions [56-84% cross-sectional area (CSA) stenosis]. The results suggest that the performance of conductance catheter is dependent on catheter size and severity of stenosis more significantly for 0.9 mm than for 0.35 mm catheter. Specifically, the time of detection of 95% of injected saline solution at the detection electrodes was shown to range from 0.67 to 3.7 s and 0.82 to 0.94 s for 0.9 mm and 0.35 mm catheter, respectively. The results also suggest that the detection electrodes of conductance catheter should be placed outside of flow recirculation region distal to the stenosis to minimize the detection time. Finally, the simulations show that the accuracy in distal CSA measurements, however, is not significantly altered by whether the position of detection electrodes is inside or outside of recirculation zone (error was within 12% regardless of detection electrodes position). The results were experimentally validated for one lesion geometry and the simulation results are within 8% of actual measurements. The simulation of conductance catheter injection method may lead to further optimization of device and method for accurate sizing of diseased coronary arteries, which has clinical relevance to percutaneous intervention.     

Numerical simulation of cardiovascular dynamics with different types of VAD assistance

A variety of methods by which mechanical circulatory support (MCS) can be provided have been described. However, the haemodynamic benefits of the different methods have not been adequately quantified. The aim of this paper is to compare the haemodynamic effects of six forms of MCS by numerical simulation. Three types of ventricular assist device (VAD) are studied: positive displacement; impeller and a novel reciprocating-valve design. Similarly, three pumping modes are modelled: constant flow; counterpulsation and copulsation. The cardiovascular system is modelled using an approach developed previously, using the concentrated parameter method by considering flow resistance, vessel elasticity and inertial effects of blood in individual conduit segments. The dynamic modelling of displacement and impeller pumps is represented by VAD inlet/outlet flow-rate changes. The dynamics of the reciprocating-valve pump is modelled with a specified displacement profile. Results show that in each simulation, the physiological variables of mean arterial pressure and systemic flow are adequately maintained. Modulation of the impeller pump flow profile produces a small (5 mmHg) oscillatory component to arterial pressure, whereas the displacement and reciprocating-valve pumps generate substantial arterial pressure and flow pulsatility. The impeller pump requires the least power input, the reciprocating valve pump slightly more, and the displacement pump the most. The in parallel configuration of the impeller and displacement pump designs with respect to the left ventricle provides near complete unloading and can cause the aortic valve to remain closed throughout the entire cardiac cycle with the attendant risk of aortic valve leaflet fusion following prolonged support. The in series configuration of the reciprocating-valve pump avoids this shortcoming but activation must be carefully synchronized to the cardiac cycle to allow adequate coronary perfusion. The reciprocating-valve pump is associated with haemodynamic advantages and a favourable power consumption.     

Numerical study to evaluate the effect of a surface-based sensor on arterial tonometry

Abstract

Arterial tonometry is a widely used non-invasive blood pressure measurement method. In contrast to the cuff-based method, it is possible to obtain a continuous pressure profile with respect to systolic and diastolic pressures using this method. However, due to a requirement of arterial tonometry—that a sensor needs to be placed directly above a blood vessel—placement error is inevitable if the measurement device is only capable of measuring local regions. This study assumed that the plate sensor is flexible, thus reducing the placement error. We investigated the pressure distribution along the wrist surface rather than the local region through the contact simulation between the flexible plate sensor and the wrist. As a result, we concluded that there is a unique pressure distribution for any specific wrist, regardless of the length and position of the plate, and that it is possible to measure the blood pressure using the response at the wrist surface to the pressure inside the radial artery.     

Pressure and flow in the umbilical cord

A fluid dynamic study of blood flow within the umbilical vessels of the human maternal-fetal circulatory system is considered. It is found that the umbilical coiling index (UCI) is unable to distinguish between cords of significantly varying pressure and flow characteristics, which are typically determined by the vessel curvature, torsion and length. Larger scale geometric non-uniformities superposed over the inherent coiling, including cords exhibiting width and/or local UCI variations as well as loose true knots, typically produce a small effect on the total pressure drop. Crucially, this implies that a helical geometry of mean coiling may be used to determine the steady vessel pressure drop through a more complex cord. The presence of vessel constriction, however, drastically increases the steady pressure drop and alters the flow profile. For pulsatile-flow within the arteries, the steady pressure approximates the time-averaged value with high accuracy over a wide range of cords. Furthermore, the relative peak systolic pressure measured over the period is virtually constant and approximately 25% below the equivalent straight-pipe value for a large range of non-straight vessels. Interestingly, this suggests that the presence of vessel helicity dampens extreme pressures within the arterial cycle and may provide another possible evolutionary benefit to the coiled structure of the cord.     

Volume elasticity, modulus of elasticity and compliance of normal and arteriosclerotic human aorta

In order to measure the flow-dynamical effect of arteriosclerotic changes of the vessel wall we determined volume elasticity E' and modulus of elasticity of 53 human aortae in a static p-V-test as other authors did, too. The p-V-curves are normalized to the aortic basic volume Vo, so that we could determine the haemodynamic effect of arteriosclerosis immediately from E' and. Diameter, length, and, accordingly, the basic volume of the aorta without prestressing increase significantly in aortae with severe arteriosclerosis in comparison to those without sclerosis. The volume elasticity E' as a function of the static aortic pressure has a minimum within physiological pressure range and changes into a linear function when arteriosclerosis increases. The modulus of elasticity of a normal aorta remains constant within a pressure range of 20 to 100 mm Hg and it shows a linear increase at higher pressure. The differences between Vo, E' and of aortae with and without severe arteriosclerosis, however, are highly significant.     

Numerical study of the uniformity of balloon-expandable stent deployment

Stents are small tubelike structures, implanted in coronary and peripheral arteries to reopen narrowed vessel sections. This endovascular intervention remains suboptimal, as the success rate is limited by restenosis. This renarrowing of a stented vessel is related to the arterial injury caused by stent-artery and balloon-artery interactions, and a local subsequent inflammatory process. Therefore, efforts to optimize the stent deployment remain very meaningful. Several authors have studied with finite element modeling the mechanical behavior of balloon-expandable stents, but none of the proposed models incorporates the folding pattern of the balloon. We developed a numerical model in which the CYPHER stent is combined with a realistic trifolded balloon. In this paper, the impact of several parameters such as balloon length, folding pattern, and relative position of the stent with respect to the balloon catheter on the free stent expansion has been investigated. Quantitative validation of the modeling strategy shows excellent agreement with data provided by the manufacturer and, therefore, the model serves as a solid basis for further investigations. The parametric analyses showed that both the balloon length and the folding pattern have a considerable influence on the uniformity and symmetry of the transient stent expansion. Consequently, this approach can be used to select the most appropriate balloon length and folding pattern for a particular stent design in order to optimize the stent deployment. Furthermore, it was demonstrated that small positioning inaccuracies may change the expansion behavior of a stent. Therefore, the placement of the stent on the balloon catheter should be accurately carried out, again in order to decrease the endothelial damage.     

Simulation of a balloon expandable stent in a realistic coronary artery—Determination of the optimum modelling strategy

Computational models of stent deployment in arteries have been widely used to shed light on various aspects of stent design and optimisation. In this context, modelling of balloon expandable stents has proved challenging due to the complex mechanics of balloon–stent interaction and the difficulties involved in creating folded balloon geometries. In this study, a method to create a folded balloon model is presented and utilised to numerically model the accurate deployment of a stent in a realistic geometry of an atherosclerotic human coronary artery. Stent deployment is, however, commonly modelled by applying an increasing pressure to the stent, thereby neglecting the balloon. This method is compared to the realistic balloon expansion simulation to fully elucidate the limitations of this procedure. The results illustrate that inclusion of a realistic balloon model is essential for accurate modelling of stent deformation and stent stresses. An alternative balloon simulation procedure is presented however, which overcomes many of the limitations of the applied pressure approach by using elements which restrain the stent as the desired diameter is achieved. This study shows that direct application of pressure to the stent inner surface may be used as an optimal modelling strategy to estimate the stresses in the vessel wall using these restraining elements and hence offer a very efficient alternative approach to numerically modelling stent deployment within complex arterial geometries. The method is limited however, in that it can only predict final stresses in the stented vessel and not those occurring during stent expansion, in which case the balloon expansion model is required.     

Mapping of the functional microcirculation in vital organs using contrast-enhanced in vivo video microscopy

A functional microcirculation is vital to the survival of mammalian tissues. In vivo video microscopy is often used in animal models to assess microvascular function, providing real-time observation of blood flow in normal and diseased tissues. To extend the capabilities of in vivo video microscopy, we have developed a contrast-enhanced system with postprocessing video analysis tools that permit quantitative assessment of microvascular geometry and function in vital organs and tissues. FITC-labeled dextran (250 kDa) was injected intravenously into anesthetized mice to provide intravascular fluorescence contrast with darker red blood cell (RBC) motion. Digitized video images of microcirculation in a variety of internal organs (e.g., lung, liver, ovary, and kidney) were processed using computer-based motion correction to remove background respiratory and cardiac movement. Stabilized videos were analyzed to generate a series of functional images revealing microhemodynamic parameters, such as plasma perfusion, RBC perfusion, and RBC supply rate. Fluorescence contrast revealed characteristic microvascular arrangements within different organs, and images generated from video sequences of liver metastases showed a marked reduction in the proportion of tumor vessels that were functional. Analysis of processed video sequences showed large reductions in vessel volume, length, and branch-point density, with a near doubling in vessel segment length. This study demonstrates that postprocessing of fluorescence contrast video sequences of the microcirculation can provide quantitative images useful for studies in a wide range of model systems.     

Conditioning domestic chickens to a magnetic anomaly

Young domestic chicks of two strains, ISA brown layers and White Leghorn X Australorps, were trained to associate a magnetic anomaly with food. This was done by feeding them in their housing boxes from a dish placed above a small coil that produced a magnetic anomaly roughly six times as strong as the local geomagnetic field. Unrewarded tests began on day 9 after hatching. In a square arena, two corresponding coils were placed underneath two opposite corners. One coil, the control coil, was double-wrapped producing no net magnetic field, while the other in the opposite corner produced a local magnetic anomaly similar to that experienced during feeding. The chicks favoured the corner with the anomaly from day 10 after hatching onward. Both strains of chickens showed this preference, indicating that they could sense the local changes in the magnetic field.     

The effect of inhibitors on the electron flow triggering photo-phobic reactions in cyanophyceae

1. Since photo-phobic reactions in the blue green alga Phormidium uncinatum seem to be triggered by changes of electron flow rates into or out of an electron pool situated in the electron transport chain between photosystem II and I, the effect of inhibitors affecting the electron transport chain has been studied.
2. Dose response curves of the phobic reaction have been measured by varying the trap energy in double beam light trap experiments with constant pairs of monochromatic light. From these dose response curves the effects of the inhibitors on both types of phobic reactions, i.e. exit reactions and entrance reactions, have been calculated.
3. Dibromothymoquinone (DBMIB) inhibits the electron transport between the electron pool and photosystem I by preventing the reoxidation of plastoquinone. The phobic entrance reaction, which results in an emptying of the light trap, is triggered by changes in the electron flow out of the pool; thus it is more effected by DBMIB than the exit reaction, which is mediated by the electron transport into the pool.
4. The phobic exit reaction, which results in accumulations in the light trap, is triggered by changes in the electron flow into the electron pool via photosystem II. 3-[3,4-dichlorophenyl]-1,1-dimethylurea (DCMU) inhibits the electron transport near photosystem II; thus it affects the exit reaction more than the entrance reaction.

     

Computational haemodynamics in two idealised cerebral wide-necked aneurysms after stent placement

Endovascular stents are being commonly used to treat cerebral wide-necked aneurysms recently. The effect of a stent placed in the parent artery is not only to protect the parent artery from occlusion, due to extension of coils and thrombosis, but also to act as flow diverter to vary the haemodynamics in the aneurysm. In this article, two idealised cerebral wide-necked aneurysms were created, one was sidewall aneurysm with curved parent vessel and the other was terminal aneurysm with the bifurcated parent vessel. The plexiglass models of the two aneurysms were 'treated' with commercial porous intravascular stents. The stented physical models were scanned by Micro-CT and the numerical models of the two idealised cerebral wide-necked aneurysms after stent placement were constructed from the scanned image files. The pulsatile flow of non-Newtonian fluid inside the models was simulated by using computational fluid dynamics package. From the simulated flow dynamics, various haemodynamic characteristics such as velocity contours, wall shear stress and oscillatory shear index (OSI) were computed. The velocity of the jet entering the sacs reduced after stent was deployed across the necks of both sidewall and terminal aneurysms; the wall shear stress on the distal neck of sidewall aneurysm reduced, the wall shear stress on the dome of the terminal aneurysm increased and the OSI on the dome of the terminal aneurysm reduced. Therefore, stent placement not only promotes thrombus formation in both aneurysm models but also reduces the regrowth risk of the sidewall aneurysm and the rupture risk of the terminal aneurysm.     

Spatial patterns of abundance and growth of Mytilus edulis on boulders in the Northern Baltic Sea proper

Small scale spatial patterns of abundance, growth and condition of the mussel Mytilus edulis on sub-littoral boulders (approx. 1–2 m high) were investigated at the island of Askö in the northern Baltic proper. The effect of side (exposed/sheltered with respect to wave action and sunlight) of boulder and position (up/down) on boulder was investigated. A large spatial variability in abundance of M. edulis between boulders and between various sites within boulders were found. The highest numbers of mussels were found on the wave exposed side, near the top of boulders. Shell growth was favoured by a sheltered side and a down position. The body condition (meat weight/shell weight) of mussels was, on the other hand, affected only by position, the condition of mussels being better at the up position. Consequently, there seems to be temporal differences in the condition for growth within a spatial position. The body condition of the mussels was best near the top of boulders in the spring, but long-term shell growth was favoured by a sheltered side and a down position. This may reflect changes in the composition and availability of food during the year with phytoplankton as the major food source during the spring bloom and resuspension of benthic production and detritus as relatively more important during the rest of the year.     

A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations

We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel–Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol’s multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system’s haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.

     

Osmotic water transport with glucose in GLUT2 and SGLT

Carrier-mediated water cotransport is currently a favored explanation for water movement against an osmotic gradient. The vestibule within the central pore of Na⁺-dependent cotransporters or GLUT2 provides the necessary precondition for an osmotic mechanism, explaining this phenomenon without carriers. Simulating equilibrative glucose inflow via the narrow external orifice of GLUT2 raises vestibular tonicity relative to the external solution. Vestibular hypertonicity causes osmotic water inflow, which raises vestibular hydrostatic pressure and forces water, salt, and glucose into the outer cytosolic layer via its wide endofacial exit. Glucose uptake via GLUT2 also raises oocyte tonicity. Glucose exit from preloaded cells depletes the vestibule of glucose, making it hypotonic and thereby inducing water efflux. Inhibiting glucose exit with phloretin reestablishes vestibular hypertonicity, as it reequilibrates with the cytosolic glucose and net water inflow recommences. Simulated Na⁺-glucose cotransport demonstrates that active glucose accumulation within the vestibule generates water flows simultaneously with the onset of glucose flow and before any flow external to the transporter caused by hypertonicity in the outer cytosolic layers. The molar ratio of water/glucose flow is seen now to relate to the ratio of hydraulic and glucose permeability rather than to water storage capacity of putative water carriers.