Showing papers on "Pulsatile flow published in 2009"

Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4– and TGF-β1–Dependent Pathway

Abstract: Objective— Hemodynamics has been associated with aortic valve (AV) inflammation, but the underlying mechanisms are not well understood. Here we tested the hypothesis that altered shear stress conditions stimulate the expression of cytokines and adhesion molecules in AV leaflets via a bone morphogenic protein (BMP)- and transforming growth fact (TGF)-β1–dependent pathway. Methods and Results— The ventricularis or aortic surface of porcine AV leaflets were exposed for 48 hours to unidirectional pulsatile and bidirectional oscillatory shear stresses ex vivo. Immunohistochemistry was performed to detect expressions of the 4 inflammatory markers VCAM-1, ICAM-1, BMP-4, and TGF-β1. Exposure of the aortic surface to pulsatile shear stress (altered hemodynamics), but not oscillatory shear stress, increased expression of the inflammatory markers. In contrast, neither pulsatile nor oscillatory shear stress affected expression of the inflammatory markers on the ventricularis surface. The shear stress–dependent expression of VCAM-1, ICAM-1, and BMP-4, but not TGF-β1, was significantly reduced by the BMP inhibitor noggin, whereas the TGF-β1 inhibitor SB431542 blocked BMP-4 expression on the aortic surface exposed to pulsatile shear stress. Conclusions— The results demonstrate that altered hemodynamics stimulates the expression of AV leaflet endothelial adhesion molecules in a TGF-β1– and BMP-4–dependent manner, providing some potential directions for future drug-based therapies for AV diseases.

Estimation of pulsatile ocular blood flow from intraocular pressure.

Abstract: A relationship has been derived between intraocular pressure and pulsatile blood flow in the eye. Measurements of intraocular pressure show a time variation that is associated with the pulsatile component of arterial pressure. Experimental results provide a means of transforming intraocular pressure changes into ocular volume changes. The eye is represented by a chamber with elastic walls, a pulsatile incoming flow of incompressible fluid (blood), and a steady outgoing flow of blood. Under these conditions, the rate of pulsatile blood flow through the eye can be approximated from the instantaneous intraocular pressure measurements. Data from a healthy human eye are used to illustrate the analysis.

Effect of flow diverter porosity on intraaneurysmal blood flow

Abstract: Background and Purpose: Growth and rupture, the two events that dominate the evolution of an intracranial aneurysm, are both dependent on intraaneurysmal flow. Decrease of intraaneurysmal flow is considered an attractive alternative for treating intracranial aneurysms by minimally invasive techniques. Such modification can be achieved by inserting stents or flow diverters alone. In the present paper, the effect of different commercial and innovative flow diverters’ porosity was studied in intracranial aneurysm models. Material and Methods: Single and stent-in-stent combination of Neuroform II as well as single and stent-in-stent combination of a new innovative, low-porosity, intracranial stent device (D1, D2, D1 + D2) were inserted in models of intracranial aneurysms under shear-driven flow and inertia-driven flow configurations. Steady and pulsating flow rates were applied using a blood-like fluid. Particle image velocimetry was used to measure velocity vector fields in the aneurysm midplane along the vessel axis. Flow and vorticity patterns, velocity and vorticity magnitudes were quantified and their value compared with the same flows in absence of the flow diverter. Results: In absence of flow diverters, a solid-like rotation could be observed in both shear-driven and inertia-driven models under steady and pulsatile flow conditions. The flow effects due to the insertion of low-porous devices such as D1 or D2 provoked a complete alteration of the flow patterns and massive reduction of velocity or vorticity magnitudes, whereas the introduction of clinically adopted high-porous devices provoked less effect in the aneurysm cavity. As expected, results showed that the lower the porosity the larger the reduction in velocity and vorticity within the aneurysm cavity. The lowest-porosity device combination (D1 and D2) reached an averaged reduction of flow parameters of 80% and 88% under steady and pulsatile flow conditions, respectively. The reduction in mean velocity and vorticity was much more significant in the shear-driven flows as compared to the inertia-driven flows. Conclusion: Although device porosity is the main parameter influencing flow reduction, other parameters such as device design and local flow conditions may influence the level of flow reduction within intracranial aneurysms.

Integrated microfluidic chip for endothelial cells culture and analysis exposed to a pulsatile and oscillatory shear stress.

Abstract: For a comprehensive understanding of cells or tissues, it is important to enable multiple studies under the controllable microenvironment of a chip. In this report, we present an integrated microfluidic cell culture platform in which endothelial cells (ECs) are under static conditions or exposed to a pulsatile and oscillatory shear stress. Through the integration of a microgap, self-contained flow loop, pneumatic pumps, and valves, the novel microfluidic chip achieved multiple functions: pulsatile and oscillatory fluid circulation, cell trapping, cell culture, the formation of ECs barrier, and adding shear stress on cells. After being introduced into the chip by gravity, the ECs arranged along the microgap with the help of hydrodynamic forces and grew in the microchannel for more than 7 days. The cells proliferated and migrated to form a barrier at the microgap to mimic the vessel wall, which separated the microenvironment into two compartments, microchannel and microchamber. An optimized pneumatic micropump was embedded to actuate flow circulation in a self-contained loop that induced a pulsatile and oscillatory shear stress at physiological levels on the ECs in the microchannel. All the analyses were performed under either static or dynamic conditions. The performance of the barrier was evaluated by the diffusion and distribution behaviors of fluorescently labeled albumin. The permeability of the barrier was comparable to that in traditional in vitro assays. The concentration gradients of the tracer formed in the microchamber can potentially be used to study cell polarization, migration and communications in the future. Additionally, the morphology and cytoskeleton of the ECs response to the pulsatile and oscillatory shear stress were analyzed. The microfluidic chip provided a multifunctional platform to enable comprehensive studies of blood vessels at the cell or tissue level.

Direct numerical simulation of the pulsatile flow through an aortic bileaflet mechanical heart valve

Abstract: This work focuses on the direct numerical simulation of the pulsatile flow through a bileaflet mechanical heart valve under physiological conditions and in a realistic aortic root geometry. The motion of the valve leaflets has been computed from the forces exerted by the fluid on the structure both being considered as a single dynamical system. To this purpose the immersed boundary method, combined with a fluid–structure interaction algorithm, has shown to be an inexpensive and accurate technique for such complex flows. Several complete flow cycles have been simulated in order to collect enough phase-averaged statistics, and the results are in good agreement with experimental data obtained for a similar configuration. The flow analysis, strongly relying on the data accessibility provided by the numerical simulation, shows how some features of the leaflets motion depend on the flow dynamics and that the criteria for the red cell damages caused by the valve need to be formulated using very detailed analysis. In particular, it is shown that the standard Eulerian computation of the Reynolds stresses, usually employed to assess the risk of haemolysis, might not be adequate on several counts: (i) Reynolds stresses are only one part of the solicitation, the other part being the viscous stresses, (ii) the characteristic scales of the two solicitations are very different and the Reynolds stresses act on lengths much larger than the red cells diameter and (iii) the Eulerian zonal assessment of the stresses completely misses the information of time exposure to the solicitation which is a fundamental ingredient for the phenomenon of haemolysis. Accordingly, the trajectories of several fluid particles have been tracked in a Lagrangian way and the pointwise instantaneous viscous stress tensor has been computed along the paths. The tensor has been then reduced to an equivalent scalar using the von Mises criterion, and the blood damage index has been evaluated following Grigioni et al. (Biomech. Model Mechanobiol., vol. 4, 2005, p. 249).

Three-dimensional computational modeling of subject-specific cerebrospinal fluid flow in the subarachnoid space.

Abstract: This study aims at investigating three-dimensional subject-specific cerebrospinal fluid (CSF) dynamics in the inferior cranial space, the superior spinal subarachnoid space (SAS), and the fourth cerebral ventricle using a combination of a finite-volume computational fluid dynamics (CFD) approach and magnetic resonance imaging (MRI) experiments. An anatomically accurate 3D model of the entire SAS of a healthy volunteer was reconstructed from high resolution T2 weighted MRI data. Subject-specific pulsatile velocity boundary conditions were imposed at planes in the pontine cistern, cerebellomedullary cistern, and in the spinal subarachnoid space. Velocimetric MRI was used to measure the velocity field at these boundaries. A constant pressure boundary condition was imposed at the interface between the aqueduct of Sylvius and the fourth ventricle. The morphology of the SAS with its complex trabecula structures was taken into account through a novel porous media model with anisotropic permeability. The governing equations were solved using finite-volume CFD. We observed a total pressure variation from -42 Pa to 40 Pa within one cardiac cycle in the investigated domain. Maximum CSF velocities of about 15 cms occurred in the inferior section of the aqueduct, 14 cms in the left foramen of Luschka, and 9 cms in the foramen of Magendie. Flow velocities in the right foramen of Luschka were found to be significantly lower than in the left, indicating three-dimensional brain asymmetries. The flow in the cerebellomedullary cistern was found to be relatively diffusive with a peak Reynolds number (Re)=72, while the flow in the pontine cistern was primarily convective with a peak Re=386. The net volumetric flow rate in the spinal canal was found to be negligible despite CSF oscillation with substantial amplitude with a maximum volumetric flow rate of 109 mlmin. The observed transient flow patterns indicate a compliant behavior of the cranial subarachnoid space. Still, the estimated deformations were small owing to the large parenchymal surface. We have integrated anatomic and velocimetric MRI data with computational fluid dynamics incorporating the porous SAS morphology for the subject-specific reconstruction of cerebrospinal fluid flow in the subarachnoid space. This model can be used as a basis for the development of computational tools, e.g., for the optimization of intrathecal drug delivery and computer-aided evaluation of cerebral pathologies such as syrinx development in syringomelia.

Flow Activation of AMP-Activated Protein Kinase in Vascular Endothelium Leads to Krüppel-Like Factor 2 Expression

Abstract: Objective— Vascular endothelial cells (ECs) confer atheroprotection at locations of the arterial tree where pulsatile laminar flow (PS) exists with a high shear stress and a large net forward direc...

High Pulsatility Flow Induces Adhesion Molecule and Cytokine mRNA Expression in Distal Pulmonary Artery Endothelial Cells

Abstract: Background: Arterial stiffening or reduced compliance of proximal pulmonary vessels has been shown to be an important predictor of outcomes in patients with pulmonary hypertension. Though current evidence indicates that arterial stiffening modulates flow pulsatility in downstream vessels and is likely related to microvascular damage in organs without extensive distributing arteries, the cellular mechanisms underlying this relationship in the pulmonary circulation are unexplored. Thus, this study was designed to examine the responses of the microvascular pulmonary endothelium to changes in flow pulsatility. Methods: A flow system was developed to reproduce arterial-like pulse flow waves with the capability of modulating flow pulsatility through regulation of upstream compliance. Pulmonary microvascular endothelial cells (PMVECs) were exposed to steady flow and pulse flow waves of varied pulsatility with varied hemodynamic energy (low: pulsatility index or PI = 1.0; medium: PI = 1.7; high: PI = 2.6) at flow frequency of 1 or 2 Hz for different durations (1 and 6 h). The mean flow rates in all the conditions were kept the same with shear stress at 14 dynes/cm2. Gene expression was evaluated by analyzing mRNA levels of adhesion molecules (ICAM-1, E-selectin), chemokine (MCP-1) and growth factor/receptor (VEGF, Flt-1) in PMVECs. Functional changes were observed with monocyte adhesion assay. Results: 1) Compared to either steady flow or low pulsatility flow, increased flow pulsatility for 1 h induced significant increases in mRNA levels of ICAM-1, E-selectin and MCP-1. 2) Sustained high pulsatility flow perfusion induced increases in ICAM, E-selectin, MCP-1, VEGF and its receptor Flt-1 expression. 3) Flow pulsatility effects on PMVECs were frequency-dependent with greater responses at 2 Hz and likely associated with the hemodynamic energy level. 4) Pulse flow waves with high flow pulsatility at 2 Hz induced leukocyte adhesion and recruitment to PMVECs. Conclusion: Increased upstream pulmonary arterial stiffness increases flow pulsatility in distal arteries and induces inflammatory gene expression, leukocyte adhesion and cell proliferation in the downstream PMVECs.

Methods for Quantifying Three-Dimensional Deformation of Arteries due to Pulsatile and Nonpulsatile Forces: Implications for the Design of Stents and Stent Grafts

Abstract: The knowledge of dynamic changes in the vascular system has become increasingly important in ensuring the safety and efficacy of endovascular devices. We developed new methods for quantifying in vivo three-dimensional (3D) arterial deformation due to pulsatile and nonpulsatile forces. A two-dimensional threshold segmentation technique combined with a level set method enabled calculation of the consistent centroid of the cross-sectional vessel lumen, whereas an optimal Fourier smoothing technique was developed to eliminate spurious irregularities of the centerline connecting the centroids. Longitudinal strain and novel metrics for axial twist and curvature change were utilized to characterize 3D deformations of the abdominal aorta, common iliac artery, and superficial femoral artery (SFA) due to musculoskeletal motion and deformations of the coronary artery due to cardiac pulsatile motion. These illustrative applications show the significance of each deformation metric, revealing significant longitudinal strain and axial twist in the SFA and coronary artery, and pronounced changes in vessel curvature in the coronary artery and in the inferior region of the SFA. The proposed methods may aid in designing preclinical tests aimed at replicating dynamic in vivo conditions in the arterial tree for the purpose of developing more durable endovascular devices including stents and stent grafts.

Effect of Non-Newtonian Behavior on Hemodynamics of Cerebral Aneurysms

Abstract: Blood flow dynamics near and within cerebral aneurysms have long been implicated in aneurysm growth and rupture. In this study, the governing equations for pulsatile flow are solved in their finite volume formulation to simulate blood flow in a range of three-dimensional aneurysm geometries. Four constitutive models are applied to investigate the influence of non-Newtonian behavior on flow patterns and fluid mechanical forces. The blood's non-Newtonian behavior is found to be more significant, in particular, vascular geometries, and to have pronounced effects on flow and fluid mechanical forces within the aneurysm. The choice of constitutive model has measurable influence on the numerical prediction of aneurysm rupture risk due to fluid stresses, though less influence than aneurysm morphology.

Method For Determining Hemodynamic Effects Of Positive Pressure Ventilation

Abstract: The present disclosure relates, in some embodiments, to devices, systems, and/or methods for collecting, processing, and/or displaying stroke volume and/or cardiac output data. For example, a device for assessing changes in cardiac output and/or stroke volume of a subject receiving airway support may comprise a processor; an airway sensor in communication with the processor, wherein the airway sensor is configured and arranged to sense pressure in the subject's airway, lungs, and/or intrapleural space over time; a blood volume sensor in communication with the processor, wherein the blood volume sensor is configured and arranged to sense pulsatile volume of blood in a tissue of the subject over time; and a display configured and arranged to display a representative of an airway pressure, a pulsatile blood volume, a photoplethysmogram, a photoplethysmogram ratio, the determined cardiac output and/or stroke volume, or combinations thereof. A method of assessing changes in cardiac output or stroke volume of a subject receiving airway support from a breathing assistance system may comprise sensing pressure in the subject's airway as a function of time, sensing pulsatile volume of blood in a tissue of the subject as a function of time, producing a photoplethysmogram from the sensed pulsatile volume, determining the ratio of the amplitude of the photoplethysmogram during inhalation to the amplitude of the photoplethysmogram during exhalation, and determining the change in cardiac output or stroke volume of the subject using the determined ratio.

Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo

Abstract: Morphogenesis of the "immature symmetric embryonic aortic arches" into the "mature and asymmetric aortic arches" involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger-Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD) India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24 Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy The highest values for WSS were noted at sites of narrowest arch diameters Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis

Importance of pulsatility in hypertensive carotid artery growth and remodeling.

Abstract: Arteries experience marked variations in blood pressure and flow during the cardiac cycle that can intensify during exercise, in disease, or with aging. Diverse observations increasingly suggest the importance of such pulsatility in arterial homeostasis and adaptations. We used a transverse aortic arch banding model to quantify chronic effects of increased pulsatile pressure and flow on wall morphology, composition, and biaxial mechanical properties in paired mouse arteries: the highly pulsatile right common carotid artery proximal to the band (RCCA-B) and the nearly normal left common carotid artery distal to the band (LCCA-B). Increased pulsatile mechanical stimuli in RCCA-B increased wall thickness compared with LCCA-B, which correlated more strongly with pulse (r* = 0.632; P < 0.01) than mean (r* = 0.020; P = 0.47) or systolic (r* = 0.466; P < 0.05) pressure. Similarly, inner diameter at mean pressure increased in RCCA-B and correlated slightly more strongly with a normalized index of blood velocity pulsatility (r* = 0.915; P < <0.001) than mean flow (r* = 0.834; P < 0.001). Increased wall thickness and luminal diameter in RCCA-B resulted from significant increases in cell number per cross-sectional area (P < 0.001) and collagen-to-elastin ratio (P < 0.05) as well as a moderate (1.7-fold) increase in glycosaminoglycan content, which appears to have contributed to the significant decrease (P < 0.001) in the in-vivo axial stretch in RCCA-B compared with LCCA-B. Changes in RCCA-B also associated with a signficant increase in monocyte chemoattractant protein-1 (P < 0.05) whereas LCCA-B did not. Pulsatile pressure and flow are thus important stimuli in the observed three-dimensional arterial adaptations, and there is a need for increased attention to the roles of both axial wall stress and adventitial remodeling.

A Mathematical Model to Evaluate Control Strategies for Mechanical Circulatory Support

Abstract: Continuous flow ventricular assist devices (VADs) for mechanical circulatory support (MCS) are generally smaller and believed to be more reliable than pulsatile VADs. However, regarding continuous flow, there are concerns about the decreased pulsatility and ventricular unloading. Moreover, pulsatile VADs offer a wider range in control strategies. For this reason, we used a computer model to evaluate whether pulsatile operation of a continuous flow VAD would be more beneficial than the standard constant pump speed. The computer model describes the left and right ventricle with one-fiber heart contraction models, and the systemic, pulmonary, and coronary circulation with lumped parameter hemodynamical models, while the heart rate is regulated with a baroreflex model. With this computer model, both normal and heart failure hemodynamics were simulated. A HeartMate II left ventricular assist device model was connected to this model, and both constant speed and pulsatile support were simulated. Pulsatile support did not solve the decreased pulsatility issue, but it did improve perfusion (cardiac index and coronary flow) and unloading (stroke work and heart rate) compared with constant speed. Also, pulsatile support would be beneficial for developing control strategies, as it offers more options to adjust assist device settings to the patient's needs. Because the mathematical model used in this study can simulate different assist device settings, it can play a valuable role in developing mechanical circulatory support control strategies.

Effect of Low-Frequency Pulsatile Flow on Expression of Osteoblastic Genes by Bone Marrow Stromal Cells

Abstract: Perfusion culture of osteoprogenitor cells is a promising means to form a bone-like extracellular matrix for tissue engineering applications, but the mechanism by which hydrodynamic shear stimulates expression of bone extracellular matrix (ECM) proteins is not understood. Osteoblasts are mechanosensitive and respond differently to steady and pulsatile flow. Therefore, to probe the effect of flow, bone marrow stromal cells (BMSCs)--cultured under osteogenic conditions--were exposed to steady or pulsatile flow at frequencies of 0.015, 0.044, or 0.074 Hz. Following 24 h of stimulus, cells were cultured statically for an additional 13 days and then analyzed for the expression of bone ECM proteins collagen 1alpha1 (Col1alpha1), osteopontin, osteocalcin (OC), and bone sialoprotein (BSP). All mRNA levels were elevated by flow, but OC and BSP were enhanced modestly with pulsatile flow. To determine if these effects were related to gene induction during flow, BMSCs were again exposed to steady or pulsatile flow for 24 h, but then analyzed immediately for expression of growth and differentiation factors bone morphogenetic proteins (BMP)-2, -4, and -7, transforming growth factor (TGF)-beta1, and vascular endothelial growth factor-A. All growth and differentiation factors were significantly elevated by flow, except BMP-4 which was suppressed. In addition, expression of BMP-2 and -7 were enhanced and TGF-beta1 suppressed by pulsatile flow relative to steady flow. These results demonstrate that pulsatile flow modulates expression of BMP-2, -7, and TGF-beta1 and suggest that enhanced expression of bone ECM proteins by pulsatile flow may be mediated through the induction of BMP-2 and -7.

3D cine displacement-encoded MRI of pulsatile brain motion

Abstract: Pulsatile brain motion is considered to be an important mechanical link between blood and cerebrospinal fluid (CSF) dynamics. Like many severe brain diseases, different types of hydrocephalus are associated with impairment of these dynamics. In this work a cine displacement-encoded imaging method employing stimulated echoes (DENSE) and a three-dimensional (3D) segmented echo-planar imaging (EPI) readout for brain motion measurements in all three spatial directions is presented. Displacement-encoded data sets of 12 healthy volunteers were analyzed with respect to reproducibility, periodicity, and intra- as well as intersubject physiological consistency. In addition, displacement values were compared with data derived from phase-contrast (PC) velocity measurements in a subset of all measured subjects. Using DENSE, displacements as low as 0.01 mm could be detected and observation of the 3D pulse pressure wave propagation was possible. Among other parameters, peak displacements in the central brain regions were measured: feet-head (FH): thalamus (0.13 +/- 0.01 mm); right-left (RL): thalamus (0.06 +/- 0.01 mm); and anterior-posterior (AP): caudate nucleus (0.05 +/- 0.01 mm).

Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement

Abstract: CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinal fluid (CSF) velocities and flow rates in the brain of six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible for pulsatile CSF flow between the cranial and the spinal subarachnoidal spaces. Simulation results include intracranial pressure gradients, solid stresses and strains, and fluid velocities throughout the cranio-spinal system. Computed velocities agree closely with our in vivo CINE-MRI CSF flow measurements. In addition to normal intracranial dynamics, our model captures the transition to acute communicating hydrocephalus. By increasing the value for reabsorption resistance in the subarachnoid villi, our model predicts that the poroelastic parenchyma matrix will be drained and the ventricles enlarge despite small transmantle pressure gradients during the transitional phase. The poroelastic simulation thus provides a plausible explanation on how reabsorption changes could be responsible for enlargement of the ventricles without large transmantle pressure gradients.

Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device.

Abstract: Instead of pulsatile ventricular assist devices an increasing number of nonpulsatile ventricular assist devices are introduced to clinical practice. The different flow characteristics of this new technique lead to alteration in shear stress on blood components, which may affect the coagulation system. Repeated von Willebrand factor analyses were performed in a patient who first was implanted with a pulsatile ventricular assist device (Thoratec HeartMate XVE), which had to be replaced after 405 days with an axial flow device (HeartMate II). During support with the pulsatile ventricular assist device there was no sign of any coagulation disorder. However, on the axial flow device acquired von Willebrand syndrome Type 2 developed. Inhibition of platelet function was also observed, which may be in part due to the von Willebrand syndrome. The HeartMate II axial flow device may induce von Willebrand syndrome, which was not observed in HeartMate XVE pulsatile ventricular assist device. Patients put on continuous flow devices should be screened for acquired von Willebrand syndrome.

Fluid–structure interaction of turbulent pulsatile flow within a flexible wall axisymmetric aortic aneurysm model

Abstract: Pulsatile turbulent flow characteristics in an axisymmetric aortic aneurysm (AA) model were analyzed numerically using a simulated physiological waveform. The transport equations were solved using the finite element formulation based on the Galerkin method of weighted residuals. A fully-coupled fluid–structure interaction (FSI) analysis was utilized in this work. We investigated the effects of turbulent flow characteristics on the distribution of wall stress and flow patterns in AA models. Wall stress distributions were calculated by computational solid stress (CSS) model, which ignores the effect of the blood flow, and the FSI model that takes into account flow and solid mechanics. Our results showed that peak wall stress and peak deformation were found to occur shortly after peak systolic flow in the FSI model and at the peak luminal pressure condition in the CSS model. Further, CSS model underestimated wall stress calculations when compared to the FSI model. There were also significant differences in the structure of flow fields between the flexible and rigid wall aneurysm models. Contour plots of kinetic energy dissipation and the application of the Kolmogorov microscale suggest that the conditions that result in red blood cell damage and platelet activation most likely occur in the near-wall region of AA during turbulent flow.

Pulsatile ocular blood flow in untreated diabetic retinopathy

Abstract: . Purpose: To measure the pulsatile component of total ocular blood flow in patients with untreated diabetic retinopathy. Subjects and Methods: An adapted pneumotonometer attached to a slit-lamp biomicroscope. 82 age-matched subjects divided into 4 groups: non-diabetic controls (n = 22); diabetics with no clinical retinopathy (n = 20); background diabetic retinopathy (n = 20); pre-proliferative/proliferative diabetic retinopathy (n = 20). Results: The mean pulsatile ocular blood flow values were found to be increased in all grades of diabetic retinopathy (no retinopathy 818 μl/min, background 1015 μl/min, pre-proliferative/proliferative 1097 μl/min) compared to the control group (644 μl/min). These pulsatile ocular blood flow values were significantly higher (p<0.05) in the background and pre-proliferative/proliferate retinopathy groups compared to controls. Pulse volume and pulse amplitude were also higher in the diabetic subjects. Mean arterial blood pressure did not differ across the groups studied. Conclusion: Pulsatile ocular blood flow was found to be higher in diabetics compared to controls and appears to increase as the severity of retinopathy progresses. Such a hyperdynamic circulation may contribute to the pathogenesis of diabetic eye disease.

Recent advances in oral pulsatile drug delivery.

Abstract: Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.