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The dynamics of pulsatile flow in distensible model arteries.

Deposits and blockages are often found in the carotid, coronary, renal and femoral arteries. This paper deals with laser-Doppler velocity measurements in models of bifurcations of the human femoral arteries. Several models were prepared for the studies: a simplified 35 degrees glass model, two elastic-silicone-rubber models with a wall thickness of 1 mm and 2 mm, and true-to-scale rigid and elastic models. These measurements give a clearer picture of how hemodynamics influences the formation of atherosclerotic plaques where there is a hardening of the arterial walls and a loss of elasticity. In addition to the effects of elasticity, the influence of the flow's pulsatility were studied. The measurements were done in steady and pulsatile flow. From the velocity measurements the shear stresses were calculated.

Arteries↗

Better preservation of endothelial function and decreased activation of the fetal renin-angiotensin pathway with the use of pulsatile flow during experimental fetal bypass.

OBJECTIVE: Pulsatile flow was shown to overcome the progressive rise in peripheral and placental vascular resistances observed during steady-flow bypass, this rise being counteracted by inhibition of nitric oxide synthase. This study quantifies the release of endothelial vasoactive substances during a 60-minute in utero model of fetal bypass. METHODS: Fetuses were randomly allocated into 1 of 2 groups (steady flow, n = 8, or pulsatile flow, n = 13) and subjected to bypass through central cannulation and perfusion with either a centrifugal or pulsatile (125 beats x min(-1)) blood pump. RESULTS: Lactate concentration was high, starting at fetal exteriorization and increasing during fetal preparation in the 2 groups. Once bypass was established, the rise was significant only in the steady-flow group. Plasma nitric oxide metabolites, similar before bypass, reached higher levels during pulsatile flow at the end of bypass (99+/-9 vs. 82+/-23 micromol x L(-1); P =.037). Levels of urinary nitric oxide metabolites were significantly higher in the pulsatile-flow than in the steady-flow group (764+/-143 vs. 508+/-240 micromol x L(-1); P =.005). Plasma cyclic guanosine monophosphate levels increased after 30 minutes of bypass in the pulsatile-flow group (25+/-18 vs. 12+/-8 pmol x mL(-1); P =.004), and urinary cyclic guanosine monophosphate excretion was higher in the pulsatile-flow group (517+/-450 vs. 118+/-78 pmol x mL(-1); P =.024). Plasma endothelin-1 levels increased in the 2 groups and were higher in the steady-flow group at 30 minutes (27+/-5 vs. 23+/-2 pg x mL(-1); P =.04) and 60 minutes of bypass (39+/-7 vs 32 +/- 6 pg x mL(-1); P =.04). Plasma renin concentration increased significantly during bypass only in the steady-flow group (26+/-10 vs. 57+/-42 in ng A1 x mL(-1) x h(-1); P =.04). CONCLUSIONS: Improved placental and peripheral perfusion during fetal pulsatile-flow bypass may be mediated by preservation of fetal/maternal endothelial nitric oxide biosynthetic mechanisms and/or decreased activation of the fetal renin-angiotensin pathway.

Analysis of Variance↗

Attenuation of the stress response to cardiopulmonary bypass by the addition of pulsatile flow.

The effect of pulsatile flow during cardiopulmonary bypass on the hormonal stress response was studied in 26 patients. Thirteen had routine and 13 had pulsatile bypass with an average pulse pressure of 30 mm Hg. Plasma vasopressin levels were significantly elevated during bypass in both groups, but were lower with pulsation (66 +/- 11 vs 36.3 pg/ml, p less than 0.05). Epinephrine levels increased in both groups during bypass, but were higher after bypass (1179 +/- 448 vs 713 +/- 140 pg/ml, p less than 0.05) and in the recovery room (1428 +/- 428 vs 699 +/- 155 pg/ml, p less than 0.05) in the nonpulsatile group. The same response was noted in the norepinephrine levels (924 +/- 225 vs 465 +/- 90 pg/ml, p less than 0.05; 1015 +/- 491 vs 717 +/- 112 pg/ml, p less than 0.05). There were no significant changes in renin activity in either group, but the increase after cardiopulmonary bypass was greater in the nonpulsatile group (2.0 +/- 0.7 vs 1.36 +/- 0.4 ng/ml/hr, NS). These data suggest that pulsatile flow significantly attenuates the vasopressin and catecholamine stress response to cardiopulmonary bypass. This may explain the increased flow requirements and better tissue perfusion and organ function and the decreased incidence of postoperative hypertension after bypass using pulsatile flow.

Blood Gas Analysis↗

Effects of pulsatile flow on gas transfer of membrane oxygenator: MENOX EL-4000 and Gyro C1-E3 pulsatile mode.

It is acknowledged that pulsatile flow enhances the gas exchange performance of membrane oxygenators. However, the data for currently developed oxygenators are limited. In this study, the effect of pulsatile flow was assessed utilizing the MENOX EL-4000 oxygenator. The in vitro test was performed following the Association for the Advancement of Medical Instrumentation (AAMI) standards. Pulsatile flow was produced by the Gyro C1-E3 centrifugal pump with periodical changing of the impeller speed. In Study 1, the following 3 groups were created and examined: nonpulsatile flow, pulsatile flow of 40 bpm, and pulsatile flow of 60 bpm. The blood flow rate was maintained at 3 L/min, and the V/Q ratio was 1. In Study 2, four groups were examined, nonpulsatile flow with V/Q = 1, nonpulsatile with V/Q = 2, pulsatile with V/Q = 1, and pulsatile with V/Q = 2. The blood flow rate was maintained at 4 L/min, and the pulse frequency was set at 40 bpm. In study 1, although O2 transfer was not enhanced, CO2 transfer was significantly improved (40-50%) by pulsatile flow, regardless of pulse frequency. Study 2 demonstrated that pulsatile flow resulted in improved CO2 transfer as did higher ventilation (V/Q = 2). Furthermore, even after applying higher ventilation, the pulsatile mode enhanced CO2 transfer more than the nonpulsatile mode. It was considered that the pulsatile mode induced an active secondary flow and enhanced mixing effects, and consequently CO2 transfer was improved. In conclusion, the pulsatile flow significantly enhanced the CO2 transfer of the MENOX oxygenator. It is indicated that applying the pulsatile mode is a unique and effective method to improve the gas exchange performance for a current membrane oxygenator.

Analysis of Variance↗

Responses to pulsatile flow in piglet isolated cerebral arteries.

Because cerebrovascular hemorrhage in newborns is often associated with fluctuations in cerebral blood flow, this study was designed to investigate the effects of pulsatile flow in isolated cerebral arteries from neonatal piglets. Arteries mounted on cannulas were bathed in and perfused with a physiologic saline solution. An electronic system produced pulsations, the amplitude and frequency of which were independently controlled. At constant mean transmural pressure (20 mm Hg), increasing flow in steps from 0 to 1.6 mL/min under steady flow conditions caused a biphasic response, constriction at low flow, and dilation at high flow. Under pulsatile flow conditions (pulse amplitude 16-24 mm Hg; 2 Hz), the arteries dilated upon flow initiation and continued to dilate as mean flow increased. Dilation to pulsatile flow did not depend on the level of mean flow because switching from steady to pulsatile flow at each flow step also caused dilation. Arteries dilated further upon increasing either pulse amplitude (12-28 mm Hg; 2 Hz) or frequency (16-24 mm Hg; 4 Hz). Inhibiting nitric oxide synthesis with Nomega-nitro-L-arginine or perfusing with glutaraldehyde to decrease endothelial cell deformability significantly reduced dilations to pulsatile flow and to increased amplitude and frequency. These data suggest that the arterial response to flow is highly dependent on the mode of flow. Dilation induced by initiating pulsatile flow or increasing either pulse amplitude or frequency appears to be mediated by augmented nitric oxide release as result of shear stress-induced deformation of the endothelial cells.

Animals↗

Ultrasonic backscattering from porcine whole blood of varying hematocrit and shear rate under pulsatile flow.

It was shown previously that ultrasonic scattering from whole blood varies during a flow cycle under pulsatile flow both in vitro and in vivo. It has been postulated that this cyclic variation may be associated with the dynamics of red cell aggregation because the shearing force acting on the red cell aggregates across the lumen is a function of time during a flow cycle. In all studies, the local shear rate variation as a function of time is unknown. The effect of shear rate on the red cell aggregation and, thus, on ultrasonic scattering from blood can only be merely speculated. One solution to this problem is to estimate the shear rate in a flow conduit by finite element analysis (FEA). An FEA computational fluid dynamics (CFD) tool was used to calculate local shear rate in a series of experiments in which ultrasonic backscattering from porcine whole blood under pulsatile flow was measured as a function of hematocrit and shear rate intravascularly with a 10-MHz catheter-mounted transducer in a mock flow loop. The results show that, at 20 beats per min (BPM), the magnitudes of the cyclic variation for hematocrits at 30, 40, and 50% were approximately 4 dB. However, at 60 BPM, the magnitude of cyclic variation was found to be minimal. The results also confirm previous findings that the amplitude and the timing of the peak of ultrasonic backscattering from porcine whole blood under pulsatile flow during a flow cycle are dependent upon the shear rate and hematocrit in a complicated way.

Animals↗

Cross flow ultrafiltration studies on solutions of pectin with pulsatile flow in-situ cleaning.

A study was conducted to evaluate the cross flow tubular ultrafiltration behavior of aqueous solutions of pectin. The effectiveness of pulsatile flow as a cleaning-in-place (CIP) technique to improve permeate flux was undertaken on the above mentioned solution. This investigation is part of a study to apply membrane filtration in the clarification of tropical fruit juice. The main variables, which were investigated, include the concentration of pectin, pulse frequency and amplitude. It was found that the amount of pectin in the solution significantly affects its ultrafiltration behavior. From the observed profiles, it is evident that the formation of gel layer on the membrane surface is responsible for the leveling of flux at high pressures. The presence of pectin was found to affect the properties of the solution such as viscosity, pH and the size of pectin colloid. Improvements in the permeate flux for pectin solution were obtained by employing pulsatile flow cleaning-in-place technique. Both pulse frequency and amplitude are important parameters that can improve the improvement of in-situ cleaning method. Similar to several findings reported in the literature, pulsatile flow showed significant effectiveness of about 60% higher flux when the ultrafiltration process is operated under laminar condition.

Detergents↗

Quantitative assessment of steady and pulsatile flow fields in a parallel plate flow chamber.

Steady and pulsatile flows were imaged and quantified in a parallel plate flow chamber that was designed to allow constant variation of the volumetric flow rate and to minimize pressure gradients across the width of the flow field. Results indicated that both the steady and pulsatile flow fields were uniform across the width of the flow chamber as shown by linear regression analysis. Further, the dynamic effects of the fluid pulse were transmitted almost instantaneously across the length of the flow field. These findings verify that parallel plate devices designed in this manner are suitable for delivering uniform steady and pulsatile shear stress to adherent cell populations in vitro.

Blood Flow Velocity↗

Turbulent stress measurements downstream of six mechanical aortic valves in a pulsatile flow model.

In a pulsatile flow model aortic Björk-Shiley Standard, Convex-Concave and Monostrut valves were investigated together with the Hall-Kaster (Medtronic-Hall), St Jude Medical and Starr-Edwards Silastic Ball valve using hot-film anemometry. Three-dimensional visualization of average systolic Reynolds normal stresses (RNS) reflected the design of the valves. Mean average RNS were used for comparison of the fluid dynamic performance along with Velocity Energy Ratio (VER100) and Turbulence Energy Ratio (TER) as a relative turbulence intensity for pulsatile flow. Mean average RNS ranged from 13.2 to 37.6 Nm-2 for all the valves with the highest levels for the Björk-Shiley Standard and Starr-Edwards Ball valve and lowest values for the St Jude Medical valve and with the Hall-Kaster (Medtronic-Hall), Björk-Shiley Convex-Concave and Monostrut valves in between.

Aortic Valve↗

Cardiac flow measurement by ultrafast CT: validation of continuous and pulsatile flow.

To gauge the accuracy of ultrafast CT in measuring cardiac output and myocardial perfusion in humans, measurements of continuous and pulsatile flow were made in a large asymmetrical phantom. The variation in the relationship between Hounsfield number and contrast concentration was assessed in a human thorax phantom. Radiopaque contrast medium was injected during perfusion of the phantom at a range of flow rates between 1.5 and 8 L/min. The phantom was scanned in two modes (50 and 100 ms) during continuous and pulsatile flow and with the phantom surrounded by air and by water. Flow in the tubes was calculated using indicator dilution theory, and flow in the tissue-equivalent chamber was calculated by applying first-pass distribution principles. The standard deviation of the difference between calculated and measured flow varied from 0.2 to 0.6 L/min, giving 95% limits of agreement from 0.4 to 1.2 L/min. The constant (K) relating Hounsfield unit number to iodine concentration varied widely both in different locations within the phantom and under different scan conditions (17.2-27.6 HU/mg I). Within a human thorax phantom, K varied from 14.15 to 23.18 HU/mg I and was dependent on location within the thorax phantom, the scan mode, and the cross-sectional diameter of the phantom. These data suggest that though the ultrafast CT scanner can measure continuous and pulsatile flow accurately in tubes, precise measurements of cardiac output in humans will require K to be assessed for each subject. Measurements of flow in tissue should be possible.

Cardiac Output↗

In vitro endothelialization of bioprosthetic heart valves provides a cell monolayer with proliferative capacities and resistance to pulsatile flow.

OBJECTIVES: Degeneration of bioprosthetic heart valves has been suggested to be at least partly an immunogenic reaction toward the xenogeneic tissue. An autologous endothelial lining has been proposed to overcome this problem. We examined in vitro endothelialization of such tissue and retention of endothelial cells after exposure to flow resembling the in vivo situation. METHODS: Cultured human saphenous vein endothelial cells were used to in vitro endothelialize photo-oxidized bioprosthetic heart valves. The endothelialized valves were mounted in a specially designed flow device, creating a pulsatile flow through the valve. Maintenance of a confluent cell layer and deposition of basement membrane markers were determined with immunohistochemical labeling. RESULTS: Labeling of the main components of the basement membrane, laminin and collagen type IV, was verified within 6 hours after in vitro endothelialization. Under static conditions, 4-mm wide denudations were completely re-endothelialized in 4 days, which was similar to the growth rate on gelatin-coated cell culture plastic, which served as a control material. After exposure of endothelialized valves to pulsatile flows for 24 hours (80 beats/min, 3.4 L/min), there were minimal cell losses from the bioprostheses. The cell layer adapted to the pulsatile flow, as verified by rearrangement of morphology and intracellular stress fibers. CONCLUSIONS: This study shows the feasibility of in vitro endothelialization of photo-oxidized bioprosthetic heart valves. The cells are able to withstand a pulsatile flow in vitro, to develop basement membrane-like structures, and to re-endothelialize denuded areas. This technology may be used to enhance the performance of bioprosthetic heart valve prostheses.

Basement Membrane↗

Effects of flow pulsatility on platelet adhesion to subendothelium.

Platelet adhesion in the annular perfusion system developed by Baumgartner was studied under pulsatile, oscillatory, or steady flow conditions. To investigate in what way pulsatile flow affects platelet adhesion, we developed a flow system that produces a sinusoidal laminar flow superimposed on a constant component in the annular perfusion chamber. Frequencies and amplitudes of this sinusoidal flow were in the physiological range. Pulse frequencies varied between 30 and 120 beats/minute, and different amplitudes of the wall shear rate in the range 75 to 1000 s-1 were studied. Shear rates resulting from the constant flow component were between 500 s-1 and 1800 s-1. Under these conditions, no significant differences in platelet adhesion were observed between steady flow and pulsatile flow. In the case of an oscillatory flow (absence of constant component), a clear dependence of platelet adhesion on the amplitude of the pulse was seen. These data indicate that platelet adhesion in larger blood vessels, such as the aorta and larger arteries where backflow is limited, is not essentially influenced by the pulsatility in these vessels.

Biophysical Phenomena↗

A flexible blood flow phantom capable of independently producing constant and pulsatile flow with a predictable spatial flow profile for ultrasound flow measurement validations.

The validation of the ultrasound time-domain correlation method of measuring blood flow has required the development of a flexible blood flow phantom capable of generating predictable flow profiles under a wide variety of conditions. The purpose of the phantom is to generate flow with well-known flow properties and not to mimic actual in vivo vessels. This paper describes a flow phantom which can independently generate both constant and pulsatile flow over a wide range of flow rates with a spatially fully developed laminar flow profile. It incorporates a computer-controlled pulsatile pump, which can produce different temporal pulsatile waveforms. The flow phantom also supports multiple vessels, different vessel sizes, as well as different attenuating media. The fluid most commonly used in the phantom is Sephadex mixed with water, and the probability density function of ultrasound reflected from Sephadex is experimentally determined and compared with that of blood. Examples of different constant and pulsatile flow experiments using the phantom are presented.

Adult↗

Turbulence in pulsatile flows.

Turbulence during pulsatile flow has been suggested as a possible mechanism to enhance the transport of gases during high-frequency ventilation. Experimental studies on oscillatory flow in straight, circular tubes have identified three types of flow: (a) laminar; (b) conditionally turbulent, in which high-frequency disturbances occur during the decelerating phase of the flow cycle but relaminarize by the beginning of the subsequent accelerating phase; and (c) fully turbulent flow, in which disturbances occur throughout the flow cycle. Fully turbulent flow has been observed only when a mean flow is present, and only laminar or conditionally turbulent flow has been observed for purely oscillatory flow. A critical Reynolds number based on the Stokes layer can be defined, and transition Reynolds numbers between 400 and 550 have been experimentally determined for purely oscillatory flow in a circular tube, although lower values are expected for physiological flows. There are some indications that the structure of oscillating turbulent flow is similar to steady turbulent flow, and preliminary work in our laboratory shows that the spectral content of flows during high-frequency ventilation is similar to that in steady turbulent flow.

Animals↗

Pressure drop and flow rate measurements in a human aortic bifurcation cast for steady and pulsatile flow.

Pressure drop and flow rate measurements in a rigid cast of a human aortic bifurcation under both steady and physiological pulsatile flow conditions are reported. Integral momentum and mechanical energy balances are used to calculate impedance, spatially averaged wall shear stress and viscous dissipation rate from the data. In the daughter branches, steady flow impedance is within 30% of the Poiseuille flow prediction, while pulsatile flow impedance is within a factor of 2 of fully developed, oscillatory, straight tube flow theory (Womersley theory). Estimates of wall shear stress are in accord with measurements obtained from velocity profiles. Mean pressure drop and viscous dissipation rate are elevated in pulsatile flow relative to steady flow at the mean flow rate, and the exponents of their Reynolds number dependence are in accord with available theory.

Aged↗

Nature of flow acceleration into a finite-sized orifice: steady and pulsatile flow studies on the flow convergence region using simultaneous ultrasound Doppler flow mapping and laser Doppler velocimetry.

OBJECTIVES: This study investigated the proximal centerline flow convergence region simultaneously by both color Doppler and laser Doppler velocimetry. BACKGROUND: Although numerous investigations have been performed to test the flow convergence method, to our knowledge there has yet been no experimental study using reference standard velocimetric techniques to define precisely the hydrodynamic factors involved in the accelerating flow region during steady and pulsatile flow. METHODS: Using an in vitro model that allows velocity measurements by laser Doppler velocimetry with simultaneous comparison with color Doppler results, we studied the centerline flow acceleration region proximal to orifices of various sizes (0.08 to 2.0 cm2). RESULTS: Agreement between theory and experimental velocities was good for large flow rates through small orifices only, and only at distances > 1.2 cm from the orifice. Changing the orifice shape from circular to slitlike produced no significant changes in velocity profiles. Constraining the proximal side walls caused a significant increase in proximal velocities at distances > 0.7 cm for the largest orifice only (2.0 cm2). Calculated flow rates agreed well with actual flow rates, with functional dependence on proximal distance and orifice size. Velocity profiles for pulsatile flow were similar to steady state flow profiles and could be integrated to calculate stroke volumes, which followed actual flow volumes well, although with general overestimation (y = 1.22x + 0.164, r = 0.92), most likely due to the use of all available proximal velocities. CONCLUSIONS: The accelerating proximal flow region responds to several hydrodynamic factors that can affect flow quantitation using the flow convergence method in the clinical situation.

Blood Flow Velocity↗