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Steal phenomenon in radiocephalic arteriovenous fistula. In vitro haemodynamic and electrical resistance simulation studies.

OBJECTIVE: steal phenomenon following an arteriovenous fistula (AVF) creation is characterised by retrograde flow in the artery segment distal to the anastomosis and occurs in the majority of patients with radiocephalic AVF although this rarely leads to distal ischaemia. To investigate the local haemodynamics after the creation of an AVF, a simple electrical resistance model which assumes time-independent flow was used. The applicability of this model to pulsatile flow conditions was verified using an in vitro flow circuit. The effects of stenoses in various artery segments were also investigated. DESIGN OF THE STUDY: the electrical analogue model consists of a pressure source, constant resistances that represent the resistance to flow of various arterial segments and the fistula. The stenosis was modelled by a resistor and a non-linear term is simulated by a current-controlled voltage source. In vitro experiments were performed in pulsatile and steady flow and the results were compared with electrical simulations. The effects of fistula flow and the presence and severity of a stenosis on flow distribution, particularly the direction of flow in the distal radial artery and flow into the hand were assessed. RESULTS: steady and pulsatile time-averaged flows measured in vitro compared well with the results of electrical circuit simulations for cases without a stenosis. When a stenosis was present comparisons were made only in steady flow and these show good agreement for stenoses of 75% area reduction. The direction of flow in the distal radial artery was antegrade (towards the hand) at low fistula flow and became retrograde as fistula flow increased. The presence of a severe stenosis in the brachial artery was found to have the strongest influence on flow to the hand. CONCLUSIONS: an electrical resistance model of a radiocephalic AVF has been validated with an in vitro pulsatile flow circuit. One of the benefits of this model is that it can be easily analysed using standard circuit simulation software. The model also provide insights into the possible haemodynamics consequences of creating an AVF with or without the presence of a stenosis in the arterial segments.

Arteriovenous Fistula↗

Cerebral dysfunction following extracorporeal circulation for aortocoronary bypass surgery: no differences in neuropsychological outcome after pulsatile versus nonpulsatile flow.

Nonpulsatile perfusion techniques with extracorporeal circulation for open-heart surgery and aortocoronary bypass grafting are widely used; this treatment is often followed by temporary or permanent neurological deficits. Experimental studies suggest that pulsatile flow may be of greater benefit because of its ability to ameliorate cerebral microcirculation. We therefore investigated 22 men who underwent aortocoronary bypass grafting. Patients were randomly divided into either a group undergoing nonpulsatile (n = 14) or pulsatile flow (n = 8). Neurological examinations were done prior to the operation and on the 7th postoperative day. EEG, cerebral blood flow (CBF), and the metabolic rates of O2 (CMR O2) and glucose (CMR Glucose) were measured before anaesthesia and 30 minutes after the start of extracorporeal circulation, when venous blood temperature was 26 degrees C. Postoperative neurological symptoms consisted of cranial nerve palsies, dysfunctions of the visual cortex, cerebellar symptoms, and slight arm paresis, but no differences between the two treatment groups were detected. Moreover, changes in EEG, CBF, and CMR rates during anaesthesia did not differ between the two groups. Our data suggest that pulsatile flow is not superior to the nonpulsatile perfusion technique, but to confirm this larger patient samples are required.

Adult↗

Characteristics of in vitro osteoblastic cell loading models.

Normal loading strains of 200-2000 (mu)epsilon to bone result in bending forces, generating mechanical stretch and pressure gradients in canaliculi that drive extracellular fluid flow, resulting in stress on the membranes of osteocytes, lining cells, and osteoblasts. Under excess loading, as well as during unloading (e.g., microgravity, bed rest), the fluid shift and resultant change in interstitial fluid flow may play a larger role in bone remodeling than mechanical stretch. The in vitro model systems used to investigate mechanical loading of bone generate either fluid shear, hydrostatic compression, biaxial stretch, uniaxial stretch, or a combination of two or more of these forces. The results of in vitro experiments suggest that fluid shear is a major factor affecting bone cell metabolism. Both the flow-loop apparatus (which produces pulsatile flow and uses fluid shear as its principal stimulus) and the uniaxial silicone plate stretching apparatus (which generates cyclic stretch) create a reproducible and consistent stimulus. Endpoints measured in flow experiments, however, are short term and usually short lived, and it is unknown whether these changes impact the function of differentiated osteoblasts. Endpoints measured in uniaxial stretch experiments are generally long-term-sustained effects of mechanical perturbation and more easily relatable to changes in osteoblastic activity. Biaxial stretch devices create both bending and compressive forces, resulting in different types of force on the cells, with the relative amount of each depending on the position of the cell in the device. Therefore, systems that incorporate pulsatile fluid flow or uniaxial stretch as the principal stimulus should be further developed and implemented in the study of the relationship between mechanical loading and bone response.

Bone and Bones↗

Ultra-short echo-time 2D time-of-flight MR angiography using a half-pulse excitation.

Flow-related artifacts remain a significant concern for magnetic resonance (MR) angiography because their appearance in angiograms adversely impacts accuracy in evaluation of arterial stenoses. In this paper, a half-pulse excitation scheme for improved two-dimensional time-of-flight (2D TOF) angiography is described. The proposed method eliminates the need for gradient moment nulling (of all orders), providing significant reductions in spin dephasing and consequent artifactual signal loss. Furthermore, because the post-excitation refocusing and flow compensation gradients are obviated, the achievable echo time is dramatically shortened. The half-pulse excitation is employed in conjunction with a fast radial-line acquisition, allowing ultra-short echo times on the order of 250-300 microsec. Radial-line acquisition methods also provide additional benefits for flow imaging: effective mitigation of pulsatile flow artifacts, full k-space coverage, and decreased scan times. The half-pulse excitation/radial-line sequence demonstrated improved performance in initial clinical evaluations of the carotid bifurcation when compared with a conventional 2D TOF sequence.

Action Potentials↗

In vitro hydrodynamic characteristics of DE-T2 biological heart valve prosthesis.

Our goal was to evaluate the DE-T2 biological heart valve prosthesis in our own pulse duplicator system. Pressure drop measurements were made across DE-T2 biological aortic valve size 21. All the pulsatile flow experiments were conducted in the Marmara Research Center pulse duplicator system. The pulsatile flow pressures were measured with Motorola MPX5100DP 9306 transducers, interfaced to Vishay 4270A, 4280, 4290, bridge amplifiers and Motorola System 4000. The valve DE-T2 had a vitellium ring with a central bar. The sewing ring was covered with bovine pericardium that continued to form the leaflets. A special incision was made in the pericardium at a 90 degrees angle to the central bar for the formation of two non-anatomical leaflets. The biological aortic valve prosthesis DE-T2 is similar to the natural aortic valve in systolic function. The closing volume is a little higher than the natural valve. Studies are continuing with the aim of diminishing the closing volume and searching for the ideal preservation solution for the pericardium.

Animals↗

Validation of the orifice formula for estimating effective heart valve opening area.

Interest in the Gorlin formula for estimating heart valve effective orifice area (EOA) has recently been rekindled and the formula itself has been challenged. In this validation study, explanted native heart valves, unimplanted mechanical prostheses, unimplanted bioprostheses and explanted bioprostheses have been tested in vitro in a pulsatile flow simulator. Pressures have been measured 30 mm upstream and 100 mm downstream from the plane of the valve sewing ring (to give pressure drop, pd in kPa). Flow (Q in 1 min-1) has been measured directly by electromagnetic flowmeter and orifice areas have either been taken from manufacturer supplied data (mechanical valves) or have been digitised from video images at maximum orifice (biological valves). The formula EOA = Q/(6.96 x pd 1/2) - 0.7 fitted the data with good correlation, r = 0.96 (n = 179). The orifice assumption on which this formula is based (cf. Gorlin formula) is confirmed though it is recommended that the formula should be modified to account for (i) the pressure recovery phenomenon and (ii) the fact that forward flow through a valve only occurs over a portion of the cycle in pulsatile flow. Heart rates used in the study ranged from 40 to 140 min-1, stroke volumes ranged from 20 to 114.3 ml, cardiac outputs from 2.0 to 8.0 1 min-1 and peripheral resistance from 0.1 to 1.6 kPa 1-1 min (1 - 12 mmHg l-1 min). Application of the formula was independent of the flow conditions.

Adult↗

Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro.

Intravascular stents, currently in experimental human use for recurrent arterial stenosis, are plagued by subacute thrombosis. As a therapeutic approach to stent-related thrombosis, we and others have suggested coating stents with endothelial cells before implantation. In a previous study we demonstrated the feasibility of coating stents with endothelial cells that were genetically modified to secrete large amounts of human tissue plasminogen activator. In the present study we attempted both to develop a clinically applicable protocol for stent seeding and to test whether seeded cells would remain adherent to stents after exposure to pulsatile flow. Endothelial cells were harvested from the saphenous veins of sheep with survival of the donor animals. Harvested cells were transduced with a retroviral vector containing a marker gene and seeded onto catheter-mounted stents under sterile conditions. Scanning electron microscopy revealed complete coverage of the stent surfaces by seeded cells. Stents were expanded and exposed to pulsatile flow in vitro. Substantial cell retention was observed on the lateral stent surfaces by light microscopy and scanning electron microscopy; fewer cells were seen on the luminal and abluminal surfaces. Removal of seeded cells from flow-exposed stents by trypsin digestion resulted in the recovery of approximately 70% of the seeded cells. These cells were viable and healthy as judged by their ability to proliferate to confluence with the same kinetics as control (non-flow-exposed) cells. Autologous genetically modified endothelial cells can be seeded onto catheter-mounted stents in a sterile manner, and stent deployment under flow conditions results in substantial retention of viable cells.

Animals↗

In vitro evaluation of multiple arterial stenoses using three-dimensional power Doppler angiography.

PURPOSE: The study was done to improve quantification of multiple arterial stenoses and to investigate a new imaging technique for lower limb arteries. Three-dimensional power Doppler angiography was used to quantify in vitro arterial stenoses. METHODS: We built two types of artery phantoms containing multiple stenoses. One used stenotic porcine arteries, and the other was designed to control the proximal and distal stenoses while we assessed central stenosis of a wall-less agar lumen. Three-dimensional power Doppler angiograms of the flow lumens were generated at different flow rates under steady and pulsatile flow conditions with a PowerPC 8500 computer-based three-dimensional ultrasound imaging system. This experimental system works off-line, performs three-dimensional acquisition, reconstruction, and display of ultrasound images. Images of flow lumens were compared with the measured B-mode images or the true geometry. RESULTS: This technique produces good three-dimensional angiographic images of the flow lumen, and multiple stenoses do not affect the diagnosis of arterial stenoses. With this technique, the average errors for estimating 80% and 50% area reduction stenoses were -10% and 4%, respectively. CONCLUSIONS: Three-dimensional power Doppler angiography has the potential to quantitatively grade multisegmental stenoses in lower limbs and generate a map for vasculature surgery planning.

Animals↗

Pulsatile albumin transport in large arteries: a numerical simulation study.

Albumin transport in a stenosed artery configuration is analyzed numerically under steady and pulsatile flow conditions. The flow dynamics is described applying the incompressible Navier-Stokes equations for Newtonian fluids, the mass transport is modelled using the convection diffusion equation. The boundary conditions describing the solute wall flux take into account the concept of endothelial resistance to albumin flux by means of a shear dependent permeability model based on experimental data. The study concentrates on the influence of steady and pulsatile flow patterns and of regional variations in vascular geometry on the solute wall flux and on the ratio of endothelial resistance to concentration boundary layer resistance. The numerical solution of the Navier-Stokes equations and of the transport equation applies the finite element method where stability of the convection dominated transport process is achieved by using an upwind procedure and a special subelement technique. Numerical simulations are carried out for albumin transport in a stenosed artery segment with 75 percent area reduction representing a late stage in the progression of an atherosclerotic disease. It is shown that albumin wall flux varies significantly along the arterial section, is strongly dependent upon the different flow regimes and varies considerably during a cardiac cycle. The comparison of steady results and pulsatile results shows differences up to 30 percent between time-averaged flux and steady flux in the separated flow region downstream the stenosis.

Arteries↗

Arterial stiffness: pathophysiology and clinical impact.

The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the < > of artery as a hollow structure, the elastic incremental modulus (Einc) characterizes the properties of the arterial wall biomaterials, independently of vessel geometry. As an alternative, arterial D can be evaluated by measuring the pulse wave velocity (PWV) which increases with the stiffening of arteries. Arterial stiffening increases left ventricular (LV) afterload and alters the coronary perfusion. With increased PWV, the WR impacts on the aorta during systole, increasing systolic pressures and myocardial oxygen consumption, and decreasing diastolic BP and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix (arteriosclerosis) as classically observed during aging or in arterial hypertension. The arterial stiffening estimated by changes in aortic PWV and intensity of WR are independent predictors of survival in end stage renal disease (ESRD) and general population. Improvement of arterial stiffening could be obtained by antihypertensive treatmen as observed with the calcium-channel blocker and ACE inhibitors. ACE inhibitors increased AC and reduced WR, and it has been shown that reversibility of aortic stiffening and use of ACE inhbitors had favorable independent effect on survival in hypertensive patients with advanced renal disease.

Arteries↗

The effects of time varying curvature on species transport in coronary arteries.

Alterations in mass transport patterns of low-density lipoproteins (LDL) and oxygen are known to cause atherosclerosis in larger arteries. We hypothesise that the species transport processes in coronary arteries may be affected by their physiological motion, a factor which has not been considered widely in mass transfer studies. Hence, we numerically simulated the mass transport of LDL and oxygen in an idealized moving coronary artery model under both steady and pulsatile flow conditions. A physiological inlet velocity and a sinusoidal curvature waveform were specified as velocity and wall motion boundary conditions. The results predicted elevation of LDL flux, impaired oxygen flux and low wall shear stress (WSS) along the inner wall of curvature, a predilection site for atherosclerosis. The wall motion induced changes in the velocity and WSS patterns were only secondary to the pulsatile flow effects. The temporal variations in flow and WSS due to the flow pulsation and wall motion did not affect temporal changes in the species wall flux. However, the wall motion did alter the time-averaged oxygen and LDL flux in the order of 26% and 12% respectively. Taken together, these results suggest that the wall motion may play an important role in coronary arterial transport processes and emphasise the need for further investigation.

Animals↗

Hemodynamic characterization of calcified stenotic human aortic valves before and after treatment with a novel aortic valve repair system.

BACKGROUND AND AIM OF THE STUDY: The repair of calcified stenotic aortic valves may be a viable alternative to current valve treatments for early-stage aortic valve disease. To date, evaluation of valve repair feasibility on the benchtop has not been performed. A pulsatile flow system for testing intact human aortic valves was developed to perform quantitative hemodynamic and mechanical assessment of a new aortic valve repair approach. METHODS: Intact calcified human aortic valves were divided into two groups with effective orifice area (EOA) > or =2.0 cm2 (group I, n = 6) or <2.0 cm2 (group II, n = 6). All valves were chemically debrided in stages for up to 60 min. A subset of valves in each group was also surgically debrided. At each stage, pre- and post-treatment hemodynamic assessment and video motion analysis were performed in the pulsatile flow system at multiple levels of physiological loading. Mineral removed was quantified using atomic absorption spectroscopy. RESULTS: Progressive removal of mineral with both mechanical and chemical debridement was associated with improved hemodynamic function of calcified human aortic valves. Improvements in EOA of up to 40% and decreases in transvalvular pressure gradient (deltaP) of up to 46% were seen. No clinically relevant increases in regurgitation were observed. CONCLUSION: Repair of stenotic calcified aortic valves using surgical and chemical debridement showed that removal of calcific deposits was directly associated with improvements in valve hemodynamic function. The level of improvement was proportional to the degree of aortic valve stenosis, to the use of surgical debridement, and to the duration of chemical debridement treatment. The study results suggested that aortic valve repair warrants further investigation as an alternative to current valve treatments in patients with early to mid-stage calcific aortic valve disease.

Aortic Valve Insufficiency↗

Intracranial aneurysms: flow analysis of their origin and progression.

PURPOSE: To explain the origin and growth of intracranial aneurysms using the hemodynamic data obtained from a computer simulation. MATERIALS AND METHODS: Pulsatile flow in an intracranial aneurysm cavity was numerically simulated based on physiologic pulsatile flow observed in the aorta. A finite element method was applied to solve the equations of motion and the non-Newtonian viscosity of blood was taken into account in the analysis. An angiogram of a middle cerebral artery segment with aneurysm was used for the computer modeling of blood flow within the aneurysm cavity. Local shear stress and pressure on the wall at the neck of the aneurysm as well as blood flow motions inside the cavity were calculated as a function of time for various stages in the development of the aneurysm. FINDINGS: Blood moves into the aneurysm cavity along the proximal wall of the cavity and emerges along the distal wall during the acceleration period of systole; however, during the deceleration period of systole and diastole, blood changes its flow direction, entering along the distal wall of the cavity and leaving along the proximal cavity wall. Rapid changes of blood flow direction result in rapid changes in wall shear stress and pressure at the proximal and distal walls of the cavity, rendering continuous damage to the intima at the cavity neck. These hemodynamic stresses relate to the anatomy of a particular vessel may be responsible for the initiation of aneurysm formation and subsequent progression, thrombosis and/or rupture. CONCLUSION: Computer modeling can further our understanding of factors that determine the origin and progression of intracranial aneurysms.

Blood Flow Velocity↗

Novel pulse duplicating bioreactor system for tissue-engineered vascular construct.

Cell culture in a biomimetic environment is known to improve the mechanical endurance of tissue-engineered cardiovascular components. Our goal was to generate a bioreactor that can reproduce a wide range of pulsatile flows with a completely physiological pressure profile. The morphology and biochemical properties of tissue-engineered products were also studied to test the usefulness of this novel bioreactor. The combination of an outflow valve, compliance chamber, and resistant clamps together with a balloon pumping system was able to successfully reproduce both physiological systolic and diastolic pressures. The compliance chamber was especially effective in transforming the original peaky pressure waveform into a physiological pressure profile. The tissues, cultured under a physiological pressure waveform with pulsatile flow, presented widely distributed cells in close contact with each other. They also showed significantly higher cell numbers, total protein content, and proteoglycan-glycosaminoglycan content than cultured tissues under a peaky pressure wave or under static conditions. This new bioreactor system is suitable for evaluating a favorable environment for tissue-engineered cardiovascular components.

Animals↗

Hemodynamics of the normal human carotid bifurcation: in vitro and in vivo studies.

The spatial and temporal characteristics of blood flow in the normal adult human carotid bifurcation are investigated by two different methods: in vitro pulsatile flow model experiments using laser Doppler anemometry and in vivo studies employing pulsed Doppler velocity measurements obtained with an ultrasound duplex scanner. Glass and Plexiglas models based upon arteriographic measurements were evaluated with laser Doppler anemometer methods for pulsatile flow. A similarity approach permits the model study to be geometrically and hydrodynamically accurate with respect to the human carotid bifurcation. These parallel but separate approaches were originally performed by the principal authors without knowledge of each others' work. Normal flow patterns in the proximal internal carotid artery are demonstrated to include: unidirectional, helical, transient reversal, and low velocity regions of flows. The characterization of these complex temporal and spatially variant flow fields required the high sample volume resolution afforded by the model study. Pulsed Doppler ultrasound and a novel method of positioning the sample volume permitted a qualitative description of the complex flow velocity fields in the normal human bifurcation. Results of the two methods are compared and a striking similarity between the two methods is observed for the primary and secondary flow features. The problem of associating blood flow velocity disturbances with the presence of intralumenal disease is addressed in the discussion. It is suggested that the flow disturbances associated with the normal carotid bifurcation are different from those associated with intraluminal disease and further, that the secondary flow structures can be usefully employed to establish normalcy.

Adult↗

Perfusion bioreactor for small diameter tissue-engineered arteries.

A scaleable perfusion bioreactor has been developed for tissue engineering of small diameter arterial constructs. This modular bioreactor allows for dynamic sequential seeding of smooth muscle and endothelial cells, biomechanical stimulation of cells during culture, and monitoring of tissue growth and maturation. Bovine aortic smooth muscle and endothelial cells were seeded onto porous tubular poly(glycolic acid) nonwoven scaffolds and cultured in the bioreactor under pulsatile flow conditions for up to 25 days. Cell proliferation was more than 3-fold after 4 days, smooth muscle cells expressed differentiated phenotype after 16 days, and collagen and elastin were distributed throughout the construct after 25 days of culture. In bioreactor experiments in which the construct lumen was seeded with endothelial cells by perfusion after 13 days of smooth muscle cell culture, endothelial cell seeding efficiency was 100%, and a confluent monolayer was observed in the lumen within 48 h. These data demonstrate that this perfusion bioreactor supports sequential seeding of constructs with smooth muscle and endothelial cells. Dynamic culture under pulsatile flow leads to cellular expression of differentiated function and extracellular matrix deposition toward the development of tissue-engineered arterial constructs.

Animals↗

Evaluation of stroke volume via arterial pulse pressure waveforms in neonatal lambs.

Arterial pulse waveforms contain information about stroke volume (SV) as an integral of pulsatile flow. SV estimation is accurate in adults with proper pulse pressure measurement technique. It is unclear whether the same methods are suitable in critically ill infants in the neonatal clinical setting where the fidelity of pulse pressure measurements are uncertain. We compared three pulse waveform SV methods with three systolic area SV methods in neonatal lambs in order to identify the most accurate and precise approach. Six newborn lambs were studied. Each lamb had a ligated ductus arteriosus and was instrumented to record high-fidelity pulsatile waveforms of arterial blood pressure using a transducer-tipped catheter and pulsatile flow via calibrated ultrasonic flow probe, respectively. Three steady-state hemodynamic conditions were induced experimentally: control, hypertension via infusion of angiotensin II, and hypotension by phlebotomy. Recordings of a range of SVs were made during a steady state that was interrupted by a transient period of decreasing SV, induced by momentarily increasing preload by pulmonary artery occlusion. Modification of pulse wave pressure measurement conditions, simulating an overdamped fluid-filled catheter system, were achieved by low-pass digital filtering of the original high-fidelity waveforms (high) to an 8-Hz cut-off (medium) and to a 2-Hz cut-off (low). The six SV estimates were then calibrated against flowmeter-derived SV and their accuracy and precision evaluated. Based on 6,479 waveforms, a systolic area method with pulse contour integration was the most accurate and precise. We conclude that neonatal pulse arterial waveforms embed SV information under a wide variety of hemodynamic and pressure waveform measurement conditions, and thus may be of potential clinical value in the assessment of newborn cardiovascular status.

Analysis of Variance↗

Correlation of central venous pressure with Doppler waveform of the common femoral veins.

The objects of this prospective study were to determine the nature of the flow in the right femoral vein and to correlate the flow velocity with the venous pressure measured in the right atrium. We performed 236 pulsed Doppler ultrasonographic examinations in 1 year on patients with a venous catheter with the distal tip in the right atrium. In the Doppler wave readouts we analyzed wave frequency, velocity components, and relationships among them and the existence of pulsatile flow. These parameters were then compared to the right atrium pressure. We investigated the correlation between the atrium pressure and the flow velocity obtained from the Doppler waveforms of the common femoral veins, obtaining a significant correlation (P<0.0001) with the following: the atrium systolic wave a, the atrium diastolic wave v, the pulsatility ratio (PR = Vmin/Vmax) and the pulsatility index (PI = [Vmax - Vmin] /Vavg). The receiver operating characteristic showed that the pulsed Doppler ultrasonography is not a sensitive technique in diagnosis high atrium pressures. In addition, both cardiac and respiratory phasicity of the venous wave was observed. A significant inverse relation was found between the pulsatile flow and high atrium pressure. Nonetheless, the low sensitivity of this technique does not allow the use of pulsatile Doppler ultrasonography in the common femoral vein for diagnosing increases of the atrium pressure.

Adolescent↗