Showing papers on "Pulsatile flow published in 2013"

Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice

Abstract: Current methodology to monitor pulsatile LH release in mice is limited by inadequate assay sensitivity, resulting in the need for collection of large blood volumes. Thus, assessment of pulsatile LH secretion in mice remains highly challenging, and observations are limited to adult mice. To address this, we developed a highly sensitive ELISA for assessment of mouse LH concentrations in small fractions of whole blood. We demonstrate that this assay is capable of reliably detecting LH down to a theoretical limit of 0.117 ng/mL in a 2-μL fraction of whole blood. Using an established frequent blood collection procedure, we validated the accuracy of this method by determining the pulsatile LH secretion in early-adult (10 weeks old) C57BL6/J male mice. Data demonstrate regular pulsatile release of LH, with peaks in LH secretion rarely exceeding 3 ng/mL. Moreover, assessment of LH release in Gpr54 knockout mice demonstrates the lack of pulsatile LH release after the loss of kisspeptin-mediated pubertal maturation. We next determined age-associated changes in pulsatile LH secretion by assessment of LH secretion in prepubertal (28 days old) C57BL6/J male mice and repeated assessment in the same mice in adulthood (120 days old). Data demonstrate that the rise in total LH secretion in mice after pubertal maturation occurs along with an overall rise in the pulsatile LH secretion rate. This was coupled with a significant increase in the number of LH secretory events (number of pulses). In addition, we observed a decrease in the clearance (increased half-life) and a decrease in the regularity (approximate entropy) of LH release. This method will be of wide general utility within the field of reproductive biology.

Fluid---structure interaction simulation of pulsatile ventricular assist devices

Abstract: In this paper we present a collection of fluid---structure interaction (FSI) computational techniques that enable realistic simulation of pulsatile Ventricular Assist Devices (VADs). The simulations involve dynamic interaction of air, blood, and a thin membrane separating the two fluids. The computational challenges addressed in this work include large, buckling motions of the membrane, the need for periodic remeshing of the fluid mechanics domain, and the necessity to employ tightly coupled FSI solution strategies due to the very strong added mass effect present in the problem. FSI simulation of a pulsatile VAD at realistic operating conditions is presented for the first time. The FSI methods prove to be robust, and may be employed in the assessment of current, and the development of future, pulsatile VAD designs.

Sympathetic Neural and Hemodynamic Responses to Upright Tilt in Patients With Pulsatile and Nonpulsatile Left Ventricular Assist Devices

Abstract: Background—Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First-generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are nonpulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans. Methods and Results—We evaluated patients with pulsatile (n=6) and nonpulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt while measuring hemodynamics and muscle sympathetic nerve activity. Patients with nonpulsatile devices had markedly elevated supine and upright muscle sympathetic nerve activity (mean±SD, 43±15 supine and 60±21 bursts/min at 60° head-up tilt) compared with patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, muscle sympathetic nerve activity w...

Measuring pulsatile flow in cerebral arteries using 4D phase-contrast MR imaging.

Abstract: BACKGROUND AND PURPOSE: 4D PCMRI can be used to quantify pulsatile hemodynamics in multiple cerebral arteries. The aim of this study was to compare 4D PCMRI and 2D PCMRI for assessments of pulsatil ...

Pulsatile motion of the trabecular meshwork in healthy human subjects quantified by phase-sensitive optical coherence tomography

Abstract: Aqueous leaves the anterior chamber of eye by passing through the trabecular meshwork (TM), a tissue thought to be responsible for increased outflow resistance in glaucoma. Motion assessment could permit characterization of TM biomechanical properties necessary to maintain intra-ocular pressure (IOP) within a narrow homeostatic range. In this paper, we report the first in vivo identification of TM motion in humans. We use a phase-sensitive optical coherence tomography (PhS-OCT) system with sub-nanometer sensitivity to detect and image dynamic pulse-induced TM motion. To permit quantification of TM motion and relationships we develop and apply a phase compensation algorithm permitting removal of the otherwise evitable confounding effects of bulk motion. Twenty healthy human eyes from 10 subjects are imaged. The results permit visualization of pulsatile TM motion visualization by PhS-OCT; correlation with the digital/cardiac pulse is highly significant. The correlation permits assessment of the phase lag and time delay between TM motion and the cardiac pulse. In this study, we find that the digital pulse leads the pulsatile TM motion by a mean phase of 3.53 ± 0.48 rad and a mean time of 0.5 ± 0.14 s in the fundamental frequency. A significant linear relationship is present between the TM phase lag and the heart rate (p value < 0.05). The TM phase lag is also affected by age, the relationship not quite reaching significance in the current study. PhS-OCT reveals pulse-induced motion of the TM that may provide insights into the biomechanics of the tissues involved in the regulation of IOP.

Central Pulse Pressure and Its Hemodynamic Determinants in Middle-Aged Adults With Impaired Fasting Glucose and Diabetes: The Asklepios study

Abstract: OBJECTIVE Pulse pressure (PP), a strong predictor of cardiovascular events in type 2 diabetes, is a composite measure affected by several hemodynamic factors. Little is known about the hemodynamic determinants of central PP in type 2 diabetes or whether abnormalities in central pulsatile hemodynamics are already present in individuals with impaired fasting glucose (IFG). In a population-based study, we aimed to compare central PP and its hemodynamic determinants among adults with normal fasting glucose ( n = 1654), IFG ( n = 240), and type 2 diabetes ( n = 33). RESEARCH DESIGN AND METHODS We measured carotid pressure, left ventricular outflow, aortic root diameter, carotid artery flow, and distension in order to measure various structural and hemodynamic arterial parameters. RESULTS IFG was associated with a greater mean arterial pressure (MAP) but was not associated with intrinsic aortic stiffening or abnormal aortic pulsatile indices after adjustment for MAP. After adjustment for age, sex, and MAP, type 2 diabetes was associated with a higher aortic root characteristic impedance (Zc), aortic root elastance-thickness product (Eh), and aortic root pulse wave velocity (but not aortic root diameter), a greater carotid-femoral pulse wave velocity, and lower total arterial compliance and wave reflection magnitude. Carotid size, Zc, distensibility, or Eh did not significantly differ between the groups. CONCLUSIONS Type 2 diabetes, but not IFG, is associated with greater large artery stiffness, without abnormalities in aortic root diameter or carotid stiffness. Subjects with type 2 diabetes demonstrate a decreased reflection magnitude, which may indicate an increased penetration of pulsatile energy to distal vascular beds.

Cardiac-like flow generator for long-term imaging of endothelial cell responses to circulatory pulsatile flow at microscale

Abstract: In vitro models of circulatory hemodynamics are required to mimic the microcirculation for study of endothelial cell responses to pulsatile shear stress by live cell imaging. This study reports the design, fabrication and characterisation of a microfluidic device that generates cardiac-like flow in a continuous culture system with a circulatory volume of only 2–3 μL. The device mimics a single chamber heart, with the following cardiac phases: (1) closure of the ventricle inlet valve, (2) contraction of the ventricle (systole) followed by opening of the outlet valve and (3) relaxation of the ventricle (diastole) with opening of the inlet valve whilst the outlet valve remains closed. Periodic valve states and ventricular contractions were actuated by microprocessor controlled pneumatics. The time-dependent velocity-field was characterised by micro-particle image velocimetry (μ-PIV). μ-PIV observations were used to help tune electronic timing of valve states and ventricular contractions for synthesis of an arterial pulse waveform to study the effect of pulsatile shear stress on bovine artery endothelial cells (BAECs). BAECs elongated and aligned with the direction of shear stress after 48 h of exposure to a pulsatile waveform with a maximum shear stress of 0.42 Pa. The threshold for BAECs alignment and elongation under steady (non-pulsatile) flow reported by Kadohama et al. (2006) is 0.7–1.4 Pa. These cells respond to transient shear stress because the time average shear stress of the pulse waveform to generate this morphological response was only 0.09 Pa, well below the steady flow threshold. The microfluidic pulse generator can simulate circulatory hemodynamics for live cell imaging of shear-induced signalling pathways.

Adaptation of Endothelial Cells to Physiologically-Modeled, Variable Shear Stress

Abstract: Endothelial cell (EC) function is mediated by variable hemodynamic shear stress patterns at the vascular wall, where complex shear stress profiles directly correlate with blood flow conditions that vary temporally based on metabolic demand The interactions of these more complex and variable shear fields with EC have not been represented in hemodynamic flow models We hypothesized that EC exposed to pulsatile shear stress that changes in magnitude and duration, modeled directly from real-time physiological variations in heart rate, would elicit phenotypic changes as relevant to their critical roles in thrombosis, hemostasis, and inflammation Here we designed a physiological flow (PF) model based on short-term temporal changes in blood flow observed in vivo and compared it to static culture and steady flow (SF) at a fixed pulse frequency of 13 Hz Results show significant changes in gene regulation as a function of temporally variable flow, indicating a reduced wound phenotype more representative of quiescence EC cultured under PF exhibited significantly higher endothelial nitric oxide synthase (eNOS) activity (PF: 1760±119 nmol/105 EC; SF: 1150±125 nmol/105 EC, p = 0002) and lower TNF-a-induced HL-60 leukocyte adhesion (PF: 37±6 HL-60 cells/mm2; SF: 111±18 HL-60/mm2, p = 0003) than cells cultured under SF which is consistent with a more quiescent anti-inflammatory and anti-thrombotic phenotype In vitro models have become increasingly adept at mimicking natural physiology and in doing so have clarified the importance of both chemical and physical cues that drive cell function These data illustrate that the variability in metabolic demand and subsequent changes in perfusion resulting in constantly variable shear stress plays a key role in EC function that has not previously been described

Rotary pumps and diminished pulsatility: do we need a pulse?

Abstract: Ventricular assist devices (VADs) have been successfully used as a bridge to heart transplant and destination therapy (DT) for congestive heart failure (HF) patients. Recently, continuous flow VAD (CVAD) has emerged as an attractive clinical option for long-term mechanical support of HF patients, with bridge-to-transplant outcomes comparable with pulsatile flow VAD (PVAD). Continuous flow VADs are smaller, more reliable, and less complex than the first-generation PVAD. Despite the widespread clinical use, CVAD support has been associated with gastrointestinal bleeding, hemorrhagic strokes, and aortic valve insufficiency. Speculation that diminished arterial pressure pulsatility associated with continuous flow devices may be contributing to these complications has sparked much debate over CVAD support. Studies comparing pulsatile flow and continuous flow (CF) support have presented conflicting findings, and the relevance to CVAD as DT is uncertain due to variations in device operation, support duration, and the criteria used to quantify pulsatility. Currently, there is interest in developing control algorithms for CVAD to increase the delivered pulsatility as a strategy to mitigate adverse event risks associated with CVAD therapy. There may also be the added benefit of specific control strategies for managing CVAD therapy, potentially improving the rate of myocardial recovery and successful weaning of mechanical circulatory support.

Pulse propagation by a capacitive mechanism drives embryonic blood flow

Abstract: Pulsatile flow is a universal feature of the blood circulatory system in vertebrates and can lead to diseases when abnormal. In the embryo, blood flow forces stimulate vessel remodeling and stem cell proliferation. At these early stages, when vessels lack muscle cells, the heart is valveless and the Reynolds number (Re) is low, few details are available regarding the mechanisms controlling pulses propagation in the developing vascular network. Making use of the recent advances in optical-tweezing flow probing approaches, fast imaging and elastic-network viscous flow modeling, we investigated the blood-flow mechanics in the zebrafish main artery and show how it modifies the heart pumping input to the network. The movement of blood cells in the embryonic artery suggests that elasticity of the network is an essential factor mediating the flow. Based on these observations, we propose a model for embryonic blood flow where arteries act like a capacitor in a way that reduces heart effort. These results demonstrate that biomechanics is key in controlling early flow propagation and argue that intravascular elasticity has a role in determining embryonic vascular function.

Asymmetric speed modulation of a rotary blood pump affects ventricular unloading.

Abstract: OBJECTIVES: Rotary blood pumps (RBPs) running at a constant speed are routinely used for the mechanical support of the heart in various clinical applications, from short-term use in heart-lung machines to long-term support of a failing heart. Their operating range is delineated by suction and regurgitation events, leaving limited control on the cardiac workload. This study investigates whether different ratios of systolic/diastolic support are advantageous over a constant-speed operation. METHODS: In order to effectively control the load on the heart, this study aimed at developing a pulsatile control algorithm for rotary pumps to investigate the impact of pump speed modulation during systole and diastole on the left ventricle unloading. The CentriMag TM RBP with a modified controller was implanted in four sheep via a left thoracotomy and cannulated from the ventricular apex to the descending aorta. To modulate the pump speed synchronized with the heartbeat, custom-made real-time software detected the QRS complex of the electrocardiogram and controlled the pump speed during systole and diastole. Four different speed modulations with the same average speed but different systolic and diastolic speeds were compared with the baseline and the constant speed support. Left ventricular (LV) pressure and volume, coronary flow and pump flow were analysed to examine the influence of the pump speed modulation. RESULTS: Pulsatile setting reduces the cardiac workload to 64% of the baseline and 72% of the constant speed value. Maximum unloading is obtained with the highest speed during diastole and high-pulse amplitude. End-diastolic volume in the pulsatile modes varied from 85 to 94% of the baseline and 96 to 107% of the constant speed value. Consequently, the mechanical load on the heart can be adjusted to provide assuagement, which may lead to myocardial recovery. The higher pump speed during systole results in an increase in the pulse pressure up to 140% compared with the constant speed. CONCLUSIONS: The present study is an initial step to more accurate speed modulation of RBPs to optimize the cardiac load control. To develop future control algorithms, the concept of high speed during diastole having a maximal unloading effect on the LV and high speed during systole increasing the pulse pressure is worth considering.

Impact of flow pulsatility on arterial drug distribution in stent-based therapy

Abstract: Drug-eluting stents reside in a dynamic fluid environment where the extent to which drugs are distributed within the arterial wall is critically modulated by the blood flowing through the arterial lumen. Yet several factors associated with the pulsatile nature of blood flow and their impact on arterial drug deposition have not been fully investigated. We employed an integrated framework comprising bench-top and computational models to explore the factors governing the time-varying fluid dynamic environment within the vasculature and their effects on arterial drug distribution patterns. A custom-designed bench-top framework comprising a model of a single drug-eluting stent strut and a poly-vinyl alcohol-based hydrogel as a model tissue bed simulated fluid flow and drug transport under fully apposed strut settings. Bench-top experiments revealed a relative independence between drug distribution and the factors governing pulsatile flow and these findings were validated with the in silico model. Interestingly, computational models simulating suboptimal deployment settings revealed a complex interplay between arterial drug distribution, Womersley number and the extent of malapposition. In particular, for a stent strut offset from the wall, total drug deposition was sensitive to changes in the pulsatile flow environment, with this dependence increasing with greater wall displacement. Our results indicate that factors governing pulsatile luminal flow on arterial drug deposition should be carefully considered in conjunction with device deployment settings for better utilization of drug-eluting stent therapy.

Blood flow in stenosed arteries with radially variable viscosity, peripheral plasma layer thickness and magnetic field

Abstract: A novel approach of combined mathematical and computational models has been developed to investigate the oscillatory two-layered flow of blood through arterial stenosis in the presence of a transverse uniform magnetic field applied Blood in the core region and plasma fluid in the peripheral layer region are assumed to obey the law of Newtonian fluid An analytical solution is obtained for velocity profile and volumetric flow rate in the peripheral plasma region and also wall shear stress Finite difference method is employed to solve the momentum equation for the core region The numerical solutions for velocity, flow rate and flow resistance are computed The effects of various parameters associated with the present flow problem such as radially variable viscosity, hematocrit, plasma layer thickness, magnetic field and pulsatile Reynolds number on the physiologically important flow characteristics namely velocity distribution, flow rate, wall shear stress and resistance to flow have been investigated It is observed that the velocity increases with the increase of plasma layer thickness An increase or a decrease in the velocity and wall shear stress against the increase in the value of magnetic parameter (Hartmann number) and hematocrit is dependent on the value of t An increase in magnetic field leads to an increase in the flow resistance and it decreases with the increase in the plasma layer thickness and pulsatile Reynolds number The information concerning the phase lag between the flow characteristics and how it is affected by the hematocrit, plasma layer thickness and Hartmann number has, for the first time, been added to the literature

Novel Pulsatile Diagonal Pump for Pediatric Extracorporeal Life Support System

Abstract: A novel pulsatile rotary flow pump has been used in clinical extracorporeal life support (ECLS) in Europe.The objective of this study is to evaluate the Medos Deltastream DP3 diagonal pump (Medos Medizintechnik AG, Stolberg, Germany) in a simulated pediatric ECLS system. The ECLS circuit consisted of a Medos Hilite 800LT hollow fiber membrane oxygenator (Medos Mediz- intechnik AG), a Medos Deltastream DP3 diagonal pump, a 10Fr Terumo TenderFlow Pediatric Arterial Cannula (Terumo Corporation, Tokyo, Japan), and an arterial/ venous tubing. All trials were conducted at flow rates ranging from 200-800 mL/min (in 200 mL/min increments) under a blood temperature of 35°C using human blood (hematocrit 40%). The postcannula pressure was main- tained 60 mm Hg by a Hoffman clamp. Real-time pressure and flow data were recorded using a Labview-based acqui- sition system (National Instruments, Austin, TX, USA). The results showed that the Medos Deltastream DP3 can generate effective pulsatile flow without backflow, provide higher flow rates and pressures than nonpulsatile flow, and then create surplus hemodynamic energy and more total hemodynamic energy than nonpulsatile flow. Pulsatility increased with increased speed differential values and flow rates, while the oxygenator pressure drop increased at an acceptable level. The Medos Deltastream DP3 diagonal pump can provide adequate quality of pulsatility without backflow, and generate more hemodynamic energy under pulsatile mode in a simulated pediatric ECLS sys- tem. Key Words: Pulsatile flow—Novel diagonal pump —Medos DP3—Cardiopulmonary bypass—Extracor- poreal life support—Pediatric.

Biomechanical investigation of pulsatile flow in a three-dimensional atherosclerotic carotid bifurcation model

Abstract: It is a well-established fact that atherosclerosis in carotid bifurcation depends on flow parameters such as wall shear stress, flow pulsatility, and blood pressure. However, it is still not clearly verified how atherosclerosis can become aggravated when plaque experiences a high level of shear stress during advance stages of this disease. In this paper, fluid and structural properties in idealistic geometries are analyzed by using fluid-structure interaction (FSI). From our results, the relationship among blood pressure, stenotic compression, and deformation was established. We show that a high level of compression occurs at the stenotic apex, and can potentially be responsible for plaque progression. Moreover, wall shear stress and deformation are significantly affected by the degree of stenosis. Finally, through analysis of the FSI-based simulation results, we can better understand the parameters that influence flow through a stenotic artery and plaque aggravation, and apply the knowledge for the enhancement of clinical research and prediction of treatment outcomes.

Pulsatile and steady-state hemodynamics of the human patella bone by diffuse optical spectroscopy.

Abstract: The cardiac cycle related pulsatile behavior of the absorption and scattering coefficients of diffuse light and the corresponding alterations in hemoglobin concentrations in the human patella was studied. The pulsations in scattering is considerably smaller than absorption. The difference in amplitude of absorption coefficient pulsations for different wavelengths was translated to pulsations in oxygenated and deoxygenated hemoglobin, which leads to strong pulsations in the total hemoglobin concentration and oxygen saturation. The physiological origin of the observed signals was confirmed by applying a thigh-cuff. Moreover, we have investigated the optical and physiological properties of the patella bone and their changes in response to arterial cuff occlusion.

In vitro pulsatility analysis of axial-flow and centrifugal-flow left ventricular assist devices.

Abstract: Mechanical circulatory support is an important and increasingly prevalent therapy for patients with advanced heart failure. Ventricular assist devices (VADs) are broadly distinguished as either volume-displacement (pulsatile-) or continuous-flow pumps. The advantages and disadvantages of pulsatile versus nonpulsatile blood flow have been chronicled and deliberated for decades [1,2]. However, the acceptance and increasing use of continuous-flow systems has come about by ongoing research demonstrating excellent recovery of failing end-organs and enhanced survival [3–5]. Rotary VADs have alleviated several concerns that earlier volume-displacement pumps experienced, including efficiency [6], anatomic fit [7], durability [8], hemolysis [9], and reliability [10]. Physically, the continuous-flow pumps have traded in a decrease in pulse pressure for a smaller sized device. With the lasting effects of chronic nonpulsatile flow unknown and the widespread and increasing use of these devices, examination of VAD responses to inherent fluctuations in preload and afterload and performance during moderate pulsatile-flow is clinically relevant. As the designs of CF-VADs continue to evolve, maintaining or producing pulsatile-flow is a sought-after positive feature. Quantifying the level of pulsatile-flow through a CF-VAD establishes a metric by which different devices can be compared. Pulsatility index (PI) is defined as a measurement for variability of the fluid flow rate. PI is calculated to relate devices to the level of pulsatile flow that is generated under a given condition. Some CF-VADs report PI on the system monitor and use it for speed control [11,12]. Even if PI is not reported, an estimated flow rate usually is, so it is possible to estimate PI as the amplitude in flow rate varies. We have observed clinically that various CF-VADs are capable of greater PI than others. To date, however, no reports exist that experimentally contrast multiple continuous-flow devices under pulsating-type, hence physiologic, conditions. Comparison of implanted devices involves too many variables for direct scientific analysis and if attempted would require a very large sample group to be statistically viable. A mock flow loop provides greater control over the parameters in the circulation than the in vivo situation. In vitro experiments designed to analyze VAD performance under pulsating pressure and flow will show how they compare to one another under physiologic conditions. Clinically, we are faced with real, important challenges in patient management based on both the loading (volume status) and unloading (hypertension) conditions of the ventricle. In this study we investigate the variations in in vitro pulsatility characteristics generated by four CF-VADs, two axial-flow type and two centrifugal- (or radial-) flow design.