Physiological Pulsatile Flow Research Articles

A Three-Dimensional Engineered Artery Model for In Vitro Atherosclerosis Research

The pathogenesis of atherosclerosis involves dysfunctions of vascular endothelial cells and smooth muscle cells as well as blood borne inflammatory cells such as monocyte-derived macrophages. In vitro experiments towards a better understanding of these dysfunctions are typically performed in two-dimensional cell culture systems. However, these models lack both the three-dimensional structure and the physiological pulsatile flow conditions of native arteries. We here describe the development and initial characterization of a tissue engineered artery equivalent, which is composed of human primary endothelial and smooth muscle cells and is exposed to flow in vitro. Histological analyses showed formation of a dense tissue composed of a tight monolayer of endothelial cells supported by a basement membrane and multiple smooth muscle cell layers. Both low (LDL) and high density lipoproteins (HDL) perfused through the artery equivalent were recovered both within endothelial cells and in the sub-endothelial intima. After activation of the endothelium with either tumour necrosis factor alpha (TNFα) or LDL, monocytes circulated through the model were found to adhere to the activated endothelium and to transmigrate into the intima. In conclusion, the described tissue engineered human artery equivalent model represents a significant step towards a relevant in vitro platform for the systematic assessment of pathogenic processes in atherosclerosis independently of any systemic factors.

Postsurgical Comparison of Pulsatile Hemodynamics in Five Unique Total Cavopulmonary Connections: Identifying Ideal Connection Strategies

Appropriate choice of Fontan pathway requires keen preoperative examination of angiographic anatomy. We hypothesize that surgical choices may be better informed by lessons learned from postoperative hemodynamic evaluation in different Fontan connection strategies. High-performance computational fluid dynamics is employed to evaluate hemodynamics in five unique Fontan anatomies. Our cohort included one lateral tunnel, extracardiac conduit, intraatrial conduit, intra/extracardiac conduit, and direct cavopulmonary connection (DCPC) Fontan pathway. Theoretical cardiac cycle-averaged power loss (Eloss) and hepatic flow distribution (HFD) were compared after modeling identical physiologic pulsatile caval flow and time-resolved pulmonary artery flow distribution. The Eloss was also evaluated at instants of peak inferior vena cava flow and peak superior vena cava flow to study caval anastomosis shape sensitivity on hemodynamics. Quantitative examination of Eloss and HFD revealed minimum cycle-averaged Eloss in the extracardiac conduit Fontan; however, at the cost of the poorest HFD (left pulmonary artery/right pulmonary artery= 84.5%/15.5%). In contrast, DCPC Fontan was found to have the best trade-off between mean Eloss (5.87 mW, 2.44%) and HFD (left pulmonary artery/right pulmonary artery= 38.9%/61.1%). Except for intraatrial conduit, the instantaneous superior vena cava and inferior vena cava peak flow Eloss exceeded the cycle average Eloss. The peak inferior vena cava flow Eloss of DCPC Fontan nearly equaled its cycle-averaged Eloss (∼5.69 mW). Considering cycle-averaged Eloss, HFD, and peak inferior vena cava flow Eloss, DCPC had the best hemodynamic performance. Intraatrial conduit Fontan is an efficient modification of lateral tunnel Fontan that offers possibility for excellent streamlining of inferior vena cava and superior vena cava with the pulmonary arteries.

A Novel Carotid Covered Stent Design: In Vitro Evaluation of Performance and Influence on the Blood Flow Regime at the Carotid Artery Bifurcation

In the present study, a novel carotid covered stent design has been developed. Prototypes of different geometrical design parameters have been fabricated and their performance has been evaluated in vitro under physiological pulsatile flow condition, utilizing flow visualization (dye injection), and particle image velocimetry techniques. These evaluations include the assessment of emboli prevention capability, side-branch flow preservation, and influence on the branch flow pattern and velocity field. The novel covered stents demonstrated significantly higher emboli prevention capability than the corresponding bare metal stent, while preserving more than 83% of the original flow of the external carotid artery (ECA). Flow in the ECA through these covered stents was uniform without evidence of undesirable flow recirculation and reversed flow that might predispose the vessel wall to post-stenting intimal thickening and atherosclerotic plaque formation. This study demonstrated the potential of these novel covered stent designs for the treatment of carotid atherosclerotic stenosis. However, further computational and in vivo investigations of hemodynamics, biological effects, and mechanical performance of this covered stent design is warranted.

Development of nitric oxide-eluting nanocomposite materials using nanoparticles for cardiovascular applications

Purpose: To develop nitric oxide (NO)-eluting nanocomposite biomaterials using nanoparticles conjugated with NO donors, which induce anti-thrombogenic properties in the development of cardiovascular devices. Methods: NO-releasing fumed silica nanoparticles (FSNPs) were synthesised via the reaction of S-nitrosothiol NO donors on to the surface of FSNPs. FTIR, NMR, acid titration, and Ellman's tests confirmed the attachment of NO donors on to FSNPs. NO-FSNPs were dispersed in to polyhedral oligomeric silsesquioxane-poly(carbonateurea)urethane (POSS-PCU) nanocomposite polymer at 2, 4, and 8 wt% and bypass grafts were fabricated using extrusion phase inversion techniques. NO release from grafts was measured in a physiological pulsatile flow circuit using the amperometric technique, and their biocompatibility was evaluated in whole blood as a measure of thrombogenicity. Results: The results confirmed the functionalisation of FSNPs with NO donors and release profiles that could be controlled by changing the amount of FSNPs in the polymer matrix. All FSNPs dispersed in to POSS-PCU were capable of NO elution and the optimal release profile was evident with 2 wt% NO-FSNP at physiologically relevant concentrations of ~ 8×10−10 mol cm−2 min−1 over a 7-h period. NOeluting grafts enhanced anti-thrombogenic properties when compared with controls to confirm the protective roles of NO and attenuation of thrombosis. Conclusions: This study used POSS-PCU nanocomposite, already in used in human as tracheal and lacrimal duct conduits. NO-releasing FSNPs were incorporated in to POSS-PCU, and controlled release was confirmed in vitro. NO-eluting bypass grafts with anti-thrombogenic properties represent a newgeneration ofmaterials in the development of cardiovascular devices.

Human endometrial stem cells as a useful source for cardiovascular regeneration

Purpose: To develop nitric oxide (NO)-eluting nanocomposite biomaterials using nanoparticles conjugated with NO donors, which induce anti-thrombogenic properties in the development of cardiovascular devices. Methods: NO-releasing fumed silica nanoparticles (FSNPs) were synthesised via the reaction of S-nitrosothiol NO donors on to the surface of FSNPs. FTIR, NMR, acid titration, and Ellman's tests confirmed the attachment of NO donors on to FSNPs. NO-FSNPs were dispersed in to polyhedral oligomeric silsesquioxane-poly(carbonateurea)urethane (POSS-PCU) nanocomposite polymer at 2, 4, and 8 wt% and bypass grafts were fabricated using extrusion phase inversion techniques. NO release from grafts was measured in a physiological pulsatile flow circuit using the amperometric technique, and their biocompatibility was evaluated in whole blood as a measure of thrombogenicity. Results: The results confirmed the functionalisation of FSNPs with NO donors and release profiles that could be controlled by changing the amount of FSNPs in the polymer matrix. All FSNPs dispersed in to POSS-PCU were capable of NO elution and the optimal release profile was evident with 2 wt% NO-FSNP at physiologically relevant concentrations of ~ 8×10−10 mol cm−2 min−1 over a 7-h period. NOeluting grafts enhanced anti-thrombogenic properties when compared with controls to confirm the protective roles of NO and attenuation of thrombosis. Conclusions: This study used POSS-PCU nanocomposite, already in used in human as tracheal and lacrimal duct conduits. NO-releasing FSNPs were incorporated in to POSS-PCU, and controlled release was confirmed in vitro. NO-eluting bypass grafts with anti-thrombogenic properties represent a newgeneration ofmaterials in the development of cardiovascular devices.

An airway smooth muscle cell niche under physiological pulsatile flow culture using a tubular dense collagen construct

Bioengineered tissue equivalents should provide physiologically relevant biochemical and mechanical cues to support the growth and differentiation of seeded cells. Herein, tubular dense collagen constructs (TDCCs) with collagen content comparable to native extracellular matrix were used to investigate the effect of shear stress alone (i.e. under laminar fluid flow), and shear stress in combination with circumferential strain (i.e. under pulsatile fluid flow) on the proliferation, alignment, and phenotype of three-dimensionally (3D) seeded airway smooth muscle cells (ASMCs). In addition, the effect of ASMC-mediated remodelling on TDCC matrix morphological and mechanical properties was investigated. Compared to static culture, pulsatile flow increased seeded ASMC growth by 70%, improved the homogeneity of cell distribution within the TDCCs and induced differential cellular alignment depending on the primary stimuli. Specifically, within the inner wall, where shear stress is predominant, ASMCs were aligned parallel to fluid flow direction, while within the outer wall ASMCs were aligned parallel to the circumferential strain (perpendicular to fluid flow). In contrast, under laminar flow, ASMCs were aligned parallel to fluid flow direction within both walls. Compared to laminar flow, pulsatile flow resulted in increased positive staining for α-smooth muscle actin, and in up-regulated typical ASMC contractile markers suggesting that circumferential strain modulates ASMC differentiation. Pulsatile flow also caused a 60 and 30% increase in collagen density within both acellular and cellular TDCCs, respectively, which was reflected in an increased apparent modulus. Compared to static culture, pulsatile stimulation of cellular constructs resulted in 70% higher circumferential strength. The TDCCs provide ASMC niche for greater insight into the responses of 3D seeded SMCs to physiologically equivalent in vitro dynamic conditioning.

An In Vitro Study of Pulsatile Fluid Dynamics in Intracranial Aneurysm Models Treated with Embolic Coils and Flow Diverters

Although coil embolization is one of the most effective treatments for intracranial aneurysms (ICAs), the procedure is often unsuccessful. For example, an ICA may persist after coil embolization if deployed coils fail to block the flow of blood into the aneurysm. Unfortunately, the specific flow changes that are effected by embolic coiling (and other endovascular therapies) are poorly understood, which creates a barrier to the design and execution of optimal treatments in the clinic. We present an in vitro pulsatile flow study of treated basilar tip aneurysm models that elucidates relationships between controllable treatment parameters and clinically important post-treatment fluid dynamics. We also compare fluid dynamic performance across embolic coils and more recently proposed devices (e.g., the Pipeline Embolization Device) that focus on treating ICAs by diverting rather than blocking blood flow. In agreement with previous steady flow studies, coil embolization-reduced velocity magnitude at the aneurysmal neck by greater percentages for a narrow-neck aneurysm, and reduced flow into aneurysms by greater percentages at lower parent vessel flow rates. However, flow diversion reduced flow into a wide-neck aneurysm more so than coil embolization, regardless of flow conditions. Finally, results also showed that for the endovascular devices we examined, treatment effects were generally less dramatic under physiologic pulsatile flow conditions as compared to steady flow conditions. The fluid dynamic performance data presented in this study represent the first direct in vitro comparison of coils and flow diverters in aneurysm models, and provide a novel, quantitative basis to aid in designing endovascular treatments toward specific fluid dynamic outcomes.

A bioreactor system for interfacial culture and physiological perfusion of vascularized tissue equivalents

A pivotal requirement for the generation of vascularized tissue equivalents is the development of culture systems that provide a physiological perfusion of the vasculature and tissue-specific culture conditions. Here, we present a bioreactor system that is suitable to culture vascularized tissue equivalents covered with culture media and at the air-medium interface, which is a vital stimulus for skin tissue. For the perfusion of the vascular system a new method was integrated into the bioreactor system that creates a physiological pulsatile medium flow between 80 and 120 mmHg to the arterial inflow of the equivalent's vascular system. Human dermal microvascular endothelial cells (hDMECs) were injected into the vascular system of a biological vascularized scaffold based on a decellularized porcine jejunal segment and cultured in the bioreactor system for 14 days. Histological analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining revealed that the hDMECs were able to recolonize the perfused vascular structures and expressed endothelial cell specific markers such as platelet endothelial cell adhesion molecule and von Willebrand factor. These results indicate that our bioreactor system can serve as a platform technology to generate advanced bioartificial tissues with a functional vasculature for future clinical applications.

NUMERICAL INVESTIGATION OF PULSATILE FLOW IN AN S-TYPE BYPASS GRAFT

Intimal hyperplasia developed at the end-to-side anastomosis of artery bypass is closely related to unphysiological hemodynamics. The helical flow as a normal physiological phenomenon in arteries is beneficial to endothelial damage repair. To deeply understand the physiological flow properties in a S-type bypass (StB) graft, four end-to-side bypass models including 30°, 45°, 60° conventional bypasses and a 45° StB were compared numerically under physiological pulsatile flow. The results showed that strong helical flow was observed at the distal anastomosis of StB. The distribution of hemodynamic parameters such as helicity, average wall shear stress and oscillating shear index, etc. were significantly improved at the S-type anastomosis as compared with those of three conventional models. The area-averaged normalized helicity in StB reached maxima at the moments of maximum flow rate and systolic deceleration. The hemodynamic performance in a 45° StB was improved as compared with a 30° conventional model. It is concluded that large StB anastomosis angle can be taken to achieve good hemodynamic performance while much smaller anastomosis angle has to be adopted for conventional bypass. As such, a S-type anastomosis should be a feasible choice of clinical artery bypass grafting due to its significant improvement in hemodynamic performance.

ASSESSING HEMODYNAMIC PERFORMANCES OF SMALL DIAMETER HELICAL GRAFTS: TRANSIENT SIMULATION

The present study numerically simulated the physiological pulsatile flow in helical grafts to increase understanding of its flow mechanism which may contribute to the design of better grafts. The wall-indices like time-averaged wall shear stress (WSS) and oscillatory shear index (OSI), joint with a quantitative index for helical flow by means of Lagrangian approach, were introduced as effective instruments to classify the hemodynamic performance of helical grafts. The simulation suggests that the helical geometry created amplified WSS magnitudes as well as elevated velocities near the wall. The calculated oscillatory shear index (OSI) values were never exceeded to 0.07 which is not considered physiologically significant. In addition, the strong secondary flow in helical graft helped the flow mixing between low-momentum fluid closer to the surface and high-momentum fluid at the center which brought the high-momentum fluid to the surface. Furthermore, Helicity analysis revealed that most of the fluid particles experienced counter-clockwise rotation during the whole cardiac cycle which helps to protect the graft wall from damage by reducing the laterally directed forces and keep flow stability. It concluded that a helical graft provides guaranties for the graft wall surface to get smooth and even washing by the blood and eliminates mechanical trauma to blood cells so that atherosclerotic plaques can hardly form in the graft wall.

LES of non-Newtonian physiological blood flow in a model of arterial stenosis

Large Eddy Simulation (LES) is performed to study the physiological pulsatile transition-to-turbulent non-Newtonian blood flow through a 3D model of arterial stenosis by using five different blood viscosity models: (i) Power-law, (ii) Carreau, (iii) Quemada, (iv) Cross and (v) modified-Casson. The computational domain has been chosen is a simple channel with a biological type stenosis formed eccentrically on the top wall. The physiological pulsation is generated at the inlet of the model using the first four harmonic series of the physiological pressure pulse (Loudon and Tordesillas [1]). The effects of the various viscosity models are investigated in terms of the global maximum shear rate, post-stenotic re-circulation zone, mean shear stress, mean pressure, and turbulent kinetic energy. We find that the non-Newtonian viscosity models enlarge the length of the post-stenotic re-circulation region by moving the reattachment point of the shear layer separating from the upper wall further downstream. But the turbulent kinetic energy at the immediate post-lip of the stenosis drops due to the effects of the non-Newtonian viscosity. The importance of using LES in modelling the non-Newtonian physiological pulsatile blood flow is also assessed for the different viscosity models in terms of the results of the dynamic subgrid-scale (SGS) stress Smagorinsky model constant, Cs, and the corresponding SGS normalised viscosity.

Investigation of physiological pulsatile flow in a model arterial stenosis using large-eddy and direct numerical simulations

Physiological pulsatile flow in a 3D model of arterial stenosis is investigated by using large eddy simulation (LES) technique. The computational domain chosen is a simple channel with a biological type stenosis formed eccentrically on the top wall. The physiological pulsation is generated at the inlet using the first harmonic of the Fourier series of pressure pulse. In LES, the large scale flows are resolved fully while the unresolved subgrid scale (SGS) motions are modelled using a localized dynamic model. Due to the narrowing of artery the pulsatile flow becomes transition-to-turbulent in the downstream region of the stenosis, where a high level of turbulent fluctuations is achieved, and some detailed information about the nature of these fluctuations are revealed through the investigation of the turbulent energy spectra. Transition-to-turbulent of the pulsatile flow in the post stenosis is examined through the various numerical results such as velocity, streamlines, velocity vectors, vortices, wall pressure and shear stresses, turbulent kinetic energy, and pressure gradient. A comparison of the LES results with the coarse DNS are given for the Reynolds number of 2000 in terms of the mean pressure, wall shear stress as well as the turbulent characteristics. The results show that the shear stress at the upper wall is low just prior to the centre of the stenosis, while it is maximum in the throat of the stenosis. But, at the immediate post stenotic region, the wall shear stress takes the oscillating form which is quite harmful to the blood cells and vessels. In addition, the pressure drops at the throat of the stenosis where the re-circulated flow region is created due to the adverse pressure gradient. The maximum turbulent kinetic energy is located at the post stenosis with the presence of the inertial sub-range region of slope −5/3.

An LDA and flow visualization study of pulsatile flow in an aortic bifurcation model

The structure of pulsatile flow in a rigid aortic bifurcation model was studied by means of a flow visualization technique and three-dimensional laser-Doppler anemometry. The model was made of glass, having the same shape as that of the average human aortic bifurcation. It was installed into a mock circulatory loop that generated physiological pulsatile flow. Flow separation was observed during accelerated and decelerated flow periods. Double helical flow existed inside the flow separation in the early accelerated flow period. In the decelerated flow period, disturbed flow appeared behind the separation zone. Flow was strongly disturbed during the back flow period, and then was gradually stabilized in the forward flow period. The flow separation and the disturbances released from the flow separation zone greatly influenced near-wall velocities along the lateral wall. The wave form of the near-wall velocity in the flow separation zone was much different from that observed in the aortic portion and behind the separation zone; for example, the magnitude of the negative peak velocity in the direction of the tube axis was larger than that of the positive one, and mean velocity in a cycle was very low. This abnormal phasic change of the near-wall velocity may be associated with atherogenesis. The three-dimensional velocity measurement is very useful for the detailed analysis of near-wall velocity patterns.

Quantitative myocardial perfusion magnetic resonance imaging: the impact of pulsatile flow on contrast agent bolus dispersion

Myocardial blood flow (MBF) can be quantified using T1-weighted first-pass magnetic resonance imaging (MRI) in combination with a tracer-kinetic model, like MMID4. This procedure requires the knowledge of an arterial input function which is usually estimated from the left ventricle (LV). Dispersion of the contrast agent bolus may occur between the LV and the tissue of interest. The aim of this study was to investigate the dispersion under conditions of physiological pulsatile blood flow, and to simulate its effect on MBF quantification. The dispersion was simulated in coronary arteries using a computational fluid dynamics (CFD) approach. Simulations were accomplished on straight vessels with stenosis of different degrees and shapes. The results show that dispersion is more pronounced under resting conditions than during hyperemia. Stenosis leads to a reduction of dispersion. In consequence, dispersion results in a systematic MBF underestimation between −0.4% and −9.3%. The relative MBF error depends not only on the dispersion but also on the actual MBF itself. Since MBF under rest is more underestimated than under stress, myocardial perfusion reserve is overestimated between 0.1% and 4.5%. Considering other sources of errors in myocardial perfusion MRI, systematic errors of MBF by bolus dispersion are relatively small.

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm²) but elevated to its peak during mid to late systole at about 18-20 dyn/cm². Low magnitude shear stress (<5 dyn/cm²) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

Electrocardiogram‐Synchronized Rotational Speed Change Mode in Rotary Pumps Could Improve Pulsatility

Continuous-flow left ventricular assist devices (LVADs) have greatly improved the prognosis of patients with end-stage heart failure, even if continuous flow is different from physiological flow in that it has less pulsatility. A novel pump controller of continuous-flow LVADs has been developed, which can change its rotational speed (RS) in synchronization with the native cardiac cycle, and we speculated that pulsatile mode, which increases RS just in the systolic phase, can create more pulsatility than the current system with constant RS does. The purpose of the present study is to evaluate the effect of this pulsatile mode of continuous-flow LVADs on pulsatility in in vivo settings. Experiments were performed on eight adult goats (61.7 ± 7.5 kg). A centrifugal pump, EVAHEART (Sun Medical Technology Research Corporation, Nagano, Japan), was installed by the apex drainage and the descending aortic perfusion. A pacing lead for the detection of ventricular electrocardiogram was sutured on the anterior wall of the right ventricle. In the present study, we compared pulse pressure or other parameters in the following three conditions, including Circuit-Clamp (i.e., no pump support), Continuous mode (constant RS), and Pulsatile mode (increase RS in systole). Assist rate was calculated by dividing pump flow (PF) by the sum of PF and ascending aortic flow (AoF). In continuous and pulsatile modes, these assist rates were adjusted around 80-90%. The following three parameters were used to evaluate pulsatility, including pulse pressure, dp/dt of aortic pressure (AoP), and energy equivalent pulse pressure (EEP = (∫PF*AoP dt)/(∫PF dt), mm Hg). The percent difference between EEP and mean AoP is used as an indicator of pulsatility, and normally it is around 10% of mean AoP in physiological pulse. Both pulse pressure and mean dp/dt max were decreased in continuous mode compared with clamp condition, while those were regained by pulsatile mode nearly to clamp condition (pulse pressure, clamp/continuous/pulsatile, 25.0 ± 7.6/11.7 ± 6.4/22.6 ± 9.8 mm Hg, mean dp/dt max, 481.9 ± 207.6/75.6 ± 36.2/351.1 ± 137.8 mm Hg/s, respectively). In clamp condition, %EEP was 10% higher than mean AoP (P = 0.0078), while in continuous mode, %EEP was nearly equivalent to mean AoP (N.S.). In pulsatile mode, %EEP was 9% higher than mean AoP (P = 0.038). Our newly developed pulsatile mode of continuous-flow LVADs can produce pulsatility comparable to physiological pulsatile flow. Further investigation on the effect of this novel drive mode on organ perfusion is currently ongoing.

Assessment of flow instabilities in the healthy aorta using flow‐sensitive MRI

To assess blood flow velocities and spatial distribution of aortic Reynolds numbers in vivo using flow-sensitive magnetic resonance imaging (MRI) and probe for flow instabilities along the aorta based on an empirical model for physiological pulsatile blood flow. Thirty young healthy volunteers were examined by flow-sensitive MRI at eight imaging planes distributed along the thoracic aorta. Flow, Womersley, Strouhal, Reynolds, and critical Reynolds numbers were calculated and used to assess the presence of flow instabilities. The average peak Reynolds number was higher in the ascending (≈4500) and descending aorta (≈4200) than in the aortic arch (≈3400). According to the calculated critical Reynolds numbers, flow instabilities were prominent in the ascending (14/30 volunteers) and descending aorta (22/30 volunteers) but not in the aortic arch (3/30 volunteers). A significant difference (P < 0.05) in supracritical peak Reynolds numbers was observed between genders. The supracritical Reynolds number, indicating flow instabilities, significantly correlated (P < 0.05) with body weight (r = 0.34), aortic diameter (r = 0.48), and cardiac output (r = 0.53). Flow-sensitive MRI was used to indirectly assess the presence of flow instabilities in vivo. The results in volunteers indicate the presence of flow instabilities in the young healthy aorta with a higher prevalence for men than women.

Pulse wave velocity as a diagnostic Index: The pitfalls of tethering versus stiffening of the arterial wall

Pulse wave velocity (PWV) is often used as a clinical index of aging, vascular disease, or age related hypertension. This practice is based on the assumption that a higher wave speed indicates vascular stiffening. This assumption is well grounded in the physics of pulsatile flow of an incompressible fluid where it is fully established that a pulse wave travels faster in a tube of stiffer wall, the wave speed becoming infinite in the mathematical limit of a rigid wall. However, in this paper we point out that the physical principal of higher pulse wave velocity in a stiffer tube is strictly valid only when the wall is free from outside constraints, which in the physiological setting is present in the form of tethering of the vessel wall. The use of PWV as an index of arterial stiffening may thus lose its validity if tethering is involved. A solution of the problem of vessel wall mechanics as they arise from the physiological pulsatile flow problem is presented for the purpose of resolving this issue. The vessel wall is considered to have finite thickness with or without tethering and with a range of mechanical properties ranging from viscoelastic to stiff. The results show that, indeed, while the wave speed becomes infinite in the mathematical limit of a rigid free wall, the opposite actually happens if the vessel wall is tethered. Here the wave speed actually diminishes as the degree of tethering increases. This dichotomy in the effects of tethering versus stiffening of the arterial wall may clearly lead to error in the interpretation of PWV as an index of vessel wall stiffness. In particular, a normal value of PWV may lead to the conclusion that vessel wall stiffening is absent while this value may in fact have been lowered by tethering. In other words, the diagnostic test may lead to a false negative diagnosis. Our results indicate that the reason for which PWV is lower in a tethered wall compared with that in a free wall of the same stiffness is that the radial movements of the wall are greatly reduced by tethering. More precisely, the results show that PWV depends strongly on the ratio of radial to axial displacements and that this ratio is much lower in a tethered wall than it is in a free wall of the same stiffness.

The effect of implantation orientation of a bileaflet mechanical heart valve on kinematics and hemodynamics in an anatomic aorta.

We carry out three-dimensional high-resolution numerical simulations of a bileaflet mechanical heart valve under physiologic pulsatile flow conditions implanted at different orientations in an anatomic aorta obtained from magnetic resonance imaging (MRI) of a volunteer. We use the extensively validated for heart valve flow curvilinear-immersed boundary (CURVIB) fluid-structure interaction (FSI) solver in which the empty aorta is discretized with a curvilinear, aorta-conforming grid while the valve is handled as an immersed boundary. The motion of the valve leaflets are calculated through a strongly coupled FSI algorithm implemented in conjunction with the Aitken convergence acceleration technique. We perform simulations for three valve orientations, which differ from each other by 45 deg and compare the results in terms of leaflet motion and flow field. We show that the valve implanted symmetrically relative to the symmetry plane of the ascending aorta curvature exhibits the smallest overall asymmetry in the motion of its two leaflets and lowest rebound during closure. Consequently, we hypothesize that this orientation is beneficial to reduce the chance of intermittent regurgitation. Furthermore, we find that the valve orientation does not significantly affect the shear stress distribution in the aortic lumen, which is in agreement with previous studies.

Preservation of endothelium nitric oxide release during beating heart surgery with respect to continuous flow cardiopulmonary bypass

A correlation between perfusion modality and vascular dilation induced by endothelial nitric oxide (NO) release has been pointed out in the literature; nevertheless, only a few studies deal with the analysis of patients treated by cardiac surgery. The aim of this work is to analyze endothelial NO release in patients undergoing cardiac surgery under continuous flow cardiopulmonary bypass (CPB) or pulsatile perfusion. Pulsatile devices approved for clinical CPB do not accurately reproduce the physiological flow waveform provided by the left ventricle while, on the other hand, it is important to analyze pulsatile perfusion under both physiological flow waveform and pulsatile flow CPB. Physiological pulsatile perfusion (supplied by the left ventricle) was examined in this study. A total of 16 patients undergoing cardiac surgery were enrolled in the study and divided into two groups: 8 patients were put on continuous flow CPB while the others underwent beating heart surgery. Venous blood samples were withdrawn to quantify endothelial NO release through its bioactive forms in blood. Plasma was used for the chemiluminescent detection of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), and the cellular component for electron spin resonance detection of nitrosylhemoglobin. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only in the continuous group for both NO(2)(-) and NO(x) (NO(2)(-) + NO(3)(-)) concentration (p=0.003 and p=0.016, respectively). A significant difference in the intraoperative nitrite concentration was also observed between the groups (p=0.006). Nitrosylhemoglobin concentration, although not instrumentally detectable, resulted as negligible with respect to the other NO metabolites. Despite the small number of patients belonging to each group, this significant reduction of NO(2)(-) concentration under continuous flow CPB revealed a strong dependence on endothelial NO release and plasma nitrite concentration on perfusion modality.