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Effect of anaesthesia on intraocular blood flow.

Pulsatile ocular blood flow, intraocular pressure, systemic blood pressure, and heart rate was measured in two groups of 15 patients. One received lignocaine 1.5 mg/kg intravenously prior to induction. There was a significant increase in intraocular pressure after suxamethonium, which was not associated with any rise in ocular blood flow. Both the IOP and ocular blood flow increased significantly after tracheal intubation. A rise in ocular blood flow reflects the stress response associated with intubation. Lignocaine failed to attenuate either response.

Anesthesia, General↗

Numerical modeling of pulsatile turbulent flow in stenotic vessels.

Pulsatile turbulent flow in stenotic vessels has been numerically modeled using the Reynolds-averaged Navier-Stokes equation approach. The commercially available computational fluid dynamics code (CFD), FLUENT, has been used for these studies. Two different experiments were modeled involving pulsatile flow through axisymmetric stenoses. Four different turbulence models were employed to study their influence on the results. It was found that the low Reynolds number k-omega turbulence model was in much better agreement with previous experimental measurements than both the low and high Reynolds number versions of the RNG (renormalization-group theory) k-epsilon turbulence model and the standard k-epsilon model, with regard to predicting the mean flow distal to the stenosis including aspects of the vortex shedding process and the turbulent flow field. All models predicted a wall shear stress peak at the throat of the stenosis with minimum values observed distal to the stenosis where flow separation occurred.

Animals↗

An experimental study of pulsatile pipe flow in the transition range.

The study of pulsatile flows is relevant to many areas of applications. Typical applications include aerodynamics, biofluid mechanics, wind flows, and gas transport. Transition to turbulence during pulsatile flow is physiologically and clinically important. It has been suggested as a possible mechanism to enhance the transport of gases during high-frequency ventilation, may be related to valvular regurgitation and heart murmurs and to post stenotic dilatation and aneurysms. Measurements in a pulsatile pipe flow with a superimposed mean flow are reported. Data were taken in a water flow with mean Reynolds numbers in the range of 0 < Re(m) < 3000, oscillating Reynolds numbers of 0 < Re omega < 4000, and Stokes parameter 7 < lambda < 15. Velocity profiles of various phases of the flow, condition for flow reversal, and pressure losses were measured. The adequacy of a quasi-steady-state model is discussed. Condition for transition is determined by visually inspecting velocity signals at the centerline.

Biomechanical Phenomena↗

Experimental flow studies in an elastic Y-model.

To determine the causes and history of atherosclerosis it is necessary to understand the hemodynamic parameters of blood circulation. Hemodynamic parameters play an important role in the formation of atherosclerotic plaques, especially near bends and bifurcations where the flow separates from the wall. Here the flow is laminar and non-axial with eddies, secondary flow, flow separation and stagnation points. Stenoses are found predominantly in flow separation areas. Therefore, it is important to separately study the following flow parameters: steady and pulsatile flow, wall elasticity and non-Newtonian flow behavior of blood. A simplified silicon elastic y-model simulating the human carotid artery was used for the analysis of these parameters. This model can be used for numerical studies as well. Flow was visualized at steady flow using dyes and at pulsatile flow with a photoelastic apparatus and a birefringent solution. The local axial velocity at steady and pulsatile flow was determined with a one-component Laser-Doppler-Anemometer (LDA). Pulsatile flow was generated by a piston membrane pump. A glycerin-water solution was used to simulate the Newtonian flow behavior of blood. A DMSO-Separan water solution was used to simulate the non-Newtonian flow behavior. Pulsatile flow creates higher and lower shear rates so called oscillating shear rate compare to steady flow depending on the velocity amplitude. The non-Newtonian fluid showed a markedly different flow behavior than the Newtonian fluid especially in areas of flow separation. Shear gradients were calculated from these velocity measurements using a bicubic spline interpolation. Shear stresses were calculated from these velocity shear gradients and the viscosity of the non-Newtonian fluid at these shear gradients. At special areas, high shear stresses > 10 Pa were found. The elasticity of the model wall also influences the flow behavior. The measurements showed that the characteristics of pulsatile flow and the elasticity of the model wall should be observed concomitantly. This paper presents the steady and pulsatile flow with a Newtonian and non-Newtonian fluid in an elastic model.

Arteriosclerosis↗

Flow-induced release of endothelium-derived relaxing factor during pulsatile bypass: experimental study in the fetal lamb.

OBJECTIVE: This study was initiated to test the hypothesis that fetal hemodynamic changes observed under pulsatile flow bypass might be related to the release of endothelium-derived relaxing factor through oscillating shear stress. METHODS: Normothermic bypass was instituted in utero in 21 preterm fetal lambs for a 1-hour period through the right atrium and main pulmonary artery. Ultrasonic flowmeters were positioned around the descending aorta and the umbilical artery. The circuit consisted of an oxygenator and a pump set to either continuous flow (n = 7) or pulsatile flow (n = 7) and adjusted to maintain a fetal main arterial pressure of 50 mm Hg. In seven other animals, endothelium-derived relaxing factor was blocked by a continuous infusion of N omega-nitro-L-arginine after 30 minutes of pulsatile flow. RESULTS: During the first 30 minutes of bypass, pump flows were significantly lower in the continuous-flow group than in the pulsatile-flow or blocked-flow groups (respectively, 612 +/- 144, 907 +/- 153 and 987 +/- 228 ml/min), with similar changes in aortic and umbilical flows. Systemic vascular resistances were significantly lower in the pulsatile-flow and blocked-flow groups than in the continuous-flow group (550 +/- 106 vs 821 +/- 212 dynes/sec/cm-5). However, after blockade of endothelium-derived relaxing factor, resistances increased gradually in the blocked-flow group to reach the level of that of the continuous-flow group at the end of bypass (943 +/- 77 vs 556 +/- 143 dynes/sec/cm-5 in the pulsatile-flow group). CONCLUSIONS: Blockade of endothelium-derived relaxing factor after 30 minutes of pulsatile flow returns fetal hemodynamics to continuous flow conditions. The specific inhibitor of endothelium-derived relaxing factor used in this experiment suggests that nitric oxide may be released by fetal endothelium during pulsatile bypass.

Animals↗

Numerical investigation of the non-Newtonian pulsatile blood flow in a bifurcation model with a non-planar branch.

The pulsatile flow of non-Newtonian fluid in a bifurcation model with a non-planar daughter branch is investigated numerically by using the Carreau-Yasuda model to take into account the shear thinning behavior of the analog blood fluid. The objective of this study is to deal with the influence of the non-Newtonian property of fluid and of out-of-plane curvature in the non-planar daughter vessel on wall shear stress (WSS), oscillatory shear index (OSI), and flow phenomena during the pulse cycle. The non-Newtonian property in the daughter vessels induces a flattened axial velocity profile due to its shear thinning behavior. The non-planarity deflects flow from the inner wall of the vessel to the outer wall and changes the distribution of WSS along the vessel, in particular in systole phase. Downstream of the bifurcation, the velocity profiles are shifted toward the flow divider, and low WSS and high shear stress temporal oscillations characterized by OSI occur on the outer wall region of the daughter vessels close to the bifurcation. Secondary motions become stronger with the addition of the out-of-plane curvature induced by the bending of the vessel, and the secondary flow patterns swirl along the non-planar daughter vessel. A significant difference between the non-Newtonian and the Newtonian pulsatile flow is revealed during the pulse cycle; however, reasonable agreement between the non-Newtonian and the rescaled Newtonian flow is found. Calculated results for the pulsatile flow support the view that the non-planarity of blood vessels and the non-Newtonian properties of blood are an important factor in hemodynamics and may play a significant role in vascular biology and pathophysiology.

Animals↗

Hemodynamic analysis could resolve the pulsatile blood flow controversy.

Reasons for fluctuations in the popularity of pulsatile cardiopulmonary bypass are discussed. The advantages of pulsatile flow have previously been stated in terms of physiologic parameters. This has produced a weak theoretic framework that has led to serious misunderstandings of the fundamental mechanical properties of pulsatile flow. Failure to consider these properties in the past may have allowed modified roller pumps to be accepted as "pulsatile," even though their pulsatile power outputs are small compared with those of the human heart. A fresh approach is required in which pulsatile blood flow is analyzed in terms of hemodynamic power and impedance parameters.

Animals↗

Multiphasic MR imaging: a new method for direct imaging of pulsatile CSF flow.

A new technique is described that allows for the creation of pure pulsatile flow magnetic resonance (MR) images in a single acquisition. Five to 16 electrocardiographically gated images spanning the entire cardiac cycle are obtained with use of a gradient-echo pulse sequence. The section can be varied from 4 mm thick to full thickness projection. Taken singly, each image provides direct assessment of flow direction and velocity. Subtraction of image pairs eliminates signal detected from stationary protons, producing images of pulsatile flow. In this study the technique was used to image the flow of cerebrospinal fluid (CSF) in healthy subjects and in one patient with syringohydromyelia. The data suggest that multiphasic MR imaging provides a powerful means for the noninvasive assessment of CSF pulsatile flow dynamics and may have potential clinical application for the investigation of a variety of abnormalities such as normal pressure hydrocephalus, syrinx, and spinal block.

Cerebrospinal Fluid↗

Doppler color flow mapping of simulated in vitro regurgitant jets: evaluation of the effects of orifice size and hemodynamic variables.

The spatial distribution of simulated regurgitant jets imaged by Doppler color flow mapping was evaluated under constant flow and pulsatile flow conditions. Jets were simulated through latex tubings of 3.2, 4.8, 6.35 and 7.9 mm by varying flow rates from 137 to 1,260 cc/min. Color jet area was linearly related to flow rate at each orifice (r = 0.96, SEE = 3.4; r = 0.99, SEE = 1.6; r = 0.97, SEE = 2.3; r = 0.97, SEE = 3.2, respectively), but significantly higher flow rates were required to maintain the same maximal spatial distribution of the jet at the larger regurgitant orifices. Constant flow jets were also simulated through needle orifices of 0.2, 0.5 and 1 mm, with a known total volume (5 cc) injected at varying flow rates and with differing absolute volumes injected at the same flow rate (0.2, 1.0 and 2.0 cc/s, respectively). Again, maximal color jet area was linearly related to flow rate at each orifice (r = 0.97, SEE = 2.3; r = 0.97, SEE = 2.4; r = 0.92, SEE = 3.9, respectively), but was not related to the absolute volume of regurgitation. Color encoding of regurgitant jets on Doppler color flow maps was demonstrated to be highly dependent on velocity and, hence, driving pressure, such that color encoding was obtained from a constant flow jet injected at a velocity of 4 m/s through an orifice of 0.04 mm diameter with flow rates as low as 0.008 cc/s. Mitral regurgitant jets were also simulated in a physiologic in vitro pulsatile flow model through three prosthetic valves with known regurgitant orifice sizes (0.2, 0.6 and 2.0 mm2). For each regurgitant orifice size, color jet area at each was linearly related to a regurgitant pressure drop (r = 0.98, SEE = 0.15; r = 0.97, SEE = 0.20; r = 0.97, SEE = 0.23, respectively), regurgitant stroke volume (r = 0.77, SEE = 0.55; r = 0.94, SEE = 0.30; r = 0.91, SEE = 0.41, respectively) and peak regurgitant flow rate (r = 0.98, SEE = 0.16; r = 0.97, SEE = 0.21; r = 0.93, SEE = 0.37, respectively), but the spatial distribution of the regurgitant jets was most highly dependent on the regurgitant pressure drop. Jet kinetic energy calculated from the summation of the individual pixel intensities integrated over the jet area was closely related to driving pressure (r = 0.84), but integration of the power mode area times pixel intensities provided the best estimation of regurgitant stroke volume (r = 0.80).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Ethanol inhibits basal and flow-induced vascular smooth muscle cell migration in vitro.

BACKGROUND: Alcohol consumption protects against coronary heart disease by as yet unclear mechanisms. The aim of this study was to determine the effect of ethanol on vascular smooth muscle cell (SMC) migration which plays an important role in the pathogenesis of atherosclerosis. MATERIALS AND METHODS: Cultures of human SMC under static (no flow) or pulsatile flow conditions (perfused transcapillary culture system) were pretreated in the absence or presence of ethanol (EtOH) whereupon their random migration (chemokinesis) was assessed by Transwell assay. RESULTS: Ethanol pretreatment (24 h) dose dependently inhibited migration of HuSMC from static cultures with a maximal inhibition of 60.8 +/- 4.4% observed at 40-80 mM, in the absence of any effect on cell adhesion or cell viability as assessed by trypan blue exclusion. In HuSMC exposed to pulsatile flow (0.3 to 25 ml/min, 24 h), there was a flow-dependent increase in migration ranging from a 1.3 +/- 0.16- to 2.67 +/- 0.26-fold increase, compared to static cells, concomitant with a significant increase in urokinase-type plasminogen activator (uPA) mRNA levels. Ethanol pretreatment (20-80 mM, 24 h) dose dependently inhibited the flow-induced increase in SMC migration but did not affect uPA mRNA expression. CONCLUSIONS: The inhibitory effect of ethanol on basal and flow-stimulated SMC migration may be relevant to its cardiovascular effects in vivo.

Blood Circulation↗

Constant blood flow during single-needle dialysis is unnecessary.

Single-needle (SN) dialysis employs tidal blood flow at the point of vascular access. The simplest SN systems convert this tidal flow to a pulsatile flow in the dialyser. It has been assumed that constant flow through the dialyser is necessary for optimal efficiency. Therefore SN blood circuits are designed to smooth the pulsatile flow in the dialyser to a relatively constant flow. This increase the complexity and cost of the SN system. In order to test the hypothesis that pulsatile flow results in lower clearances than constant flow, we performed measurements of clearance in vitro using pulsatile blood flow at time-averaged rates of 50-250 ml/min and tidal volumes 200-100 ml/min. These were compared with clearances using constant blood flow at the same rates. At all flow rates and at tidal volumes up to 50 ml, the clearance measurements obtained during pulsatile flow were identical to those obtained during constant flow.

Costs and Cost Analysis↗

Echogenicity variations from porcine blood II: the "bright ring" under oscillatory flow.

Echogenicity variations from porcine blood were observed in a mock flow loop under pulsatile flow in a series of experiments (Paeng et al. 2004). In this paper, oscillatory flow was generated to further investigate the cyclic and radial variation of blood echogenicity and its origin and mechanisms by several parameters, including stroke volume, stroke rate, mean steady flow and transducer angle, using a GE LOGIQ 700 Expert system. The echogenicity at the center of the tube was enhanced during acceleration and lower during deceleration, and the expansion and collapse of the "bright ring" was observed twice per cycle. The "black hole," a central echo-poor zone surrounded by a hyperechoic zone, was barely observable under oscillatory flow, and these patterns differed from those under pulsatile flow. The cyclic and radial variation of echogenicity under oscillatory flow was affected by such hemodynamic parameters as stroke volume, stroke rate and mean steady flow. It was suggested that rouleaux might be aligned at an angle of about 25 degrees relative to the tube axis during the acceleration phase, based on the experimental results reaching a maximum of the echogenicity variation at a transducer angle of 25 degrees. Radial distribution of rouleaux alignments was proposed to be another important factor to blood echogenicity variation, in addition to combined effects of shear rate and flow acceleration on erythrocyte aggregation and blood echogenicity. The weak cyclic variation of echogenicity was also observed from the porcine erythrocyte suspensions under pure oscillatory flow, but not under pulsatile flow. It is postulated that the echogenicity variations from erythrocyte suspensions are from red cell deformation.

Animals↗

Pulsatile flow-induced angiogenesis: role of G(i) subunits.

OBJECTIVE: Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity. METHODS AND RESULTS: Bovine aortic ECs were exposed to "static" or "flow" (1.2 to 67.0 mL/min, shear stress 1.4 to 19.2 dyne/cm2) conditions for 2 to 24 hours. After exposure, angiogenesis was measured as tubule formation on Matrigel, and EC migration was assessed by filter migration assay. Pulsatile flow increased angiogenesis and EC migration in a temporal and force-dependent manner, with a maximal effect at 16 hours (13.2 dyne/cm2). Pertussis toxin completely inhibited the effect of pulsatile flow on angiogenesis and migration. Transfection of ECs with inhibitory mutants of the alpha subunit of G(i)1 or G(i)3, but not G(i)2, inhibited the flow-induced angiogenic response by 61+/-2% and 32+/-6%, respectively, whereas transfection with constitutively activated mutants of the alpha subunit of G(i)1 or G(i)3, but not G(i)2, increased the flow-induced response by 202+/-23% and 70+/-4%, respectively. In contrast, inhibition of Gbetagamma by the carboxy terminal fragment of beta-adrenergic receptor kinase overexpression increased the flow-induced response by 82+/-8%. CONCLUSIONS: These results suggest that pulsatile flow stimulates angiogenesis and that this effect is mediated by activation of G(ialpha)1 or G(ialpha)3, but not Gbetagamma, subunits.

Animals↗

A theoretical model for pulsatile blood flow with applications to cerebrovascular diseases.

A solution for fully developed pulsatile flow of a couple stress fluid through a circular, rigid tube of infinite length has been obtained in the form of a Bessel-Fourier series. The velocity profiles and flow rates for different values of flow parameters have been shown graphically. It has been observed that velocity and flow rate are almost in phase with pressure gradient for low values of pulsatile Reynolds number alpha (alpha 2 = 0.1). For higher values of alpha(= 2) a phase difference of approximately 30 degrees between the velocity profile and pressure gradient has been observed. The obtained results are in good agreement with other theoretical and experimental results. The present analysis is valid for both values of alpha , i.e., alpha greater than or equal to 1 and alpha less than 1, whereas the existing analysis for pulsatile flow of couple stress fluid is valid for only alpha less than 1. The first, second, and third approximate solutions have been obtained and it is found that the convergence of the solutions is quite fast and the series could be terminated after the second term. This theoretical work could be useful in the measurement of blood flow rates, its apparent viscosity, and peripheral resistance of the circulatory system which, at present, are thought to be some of the main causes of many cerebrovascular diseases and stroke problems.U

Cerebrovascular Circulation↗

The second and third model of the flow transformed pulsatile total artificial heart.

For the purpose of future total implantation, a new pulsatile total artificial heart, a flow transformed pulsatile total artificial heart (FTPTAH), in which the continuous flow from a single centrifugal pump (CFP) was converted to pulsatile flow by switching two three-way valves that could alternately perfuse the systemic and pulmonary circulation, was proposed, and the data from the prototype model were reported. As the next step, the second model, in which a CFP and a spool valve (SV) driven with a solenoid were fabricated in one piece, was made and tested in a mock circulatory system. The system could send 4.7 L/min of pulsatile output alternately to the pulmonary artery and aorta, with 30 and 100 mmHg afterload, respectively, at 3000 rpm CFP. However, three problems were encountered: the output was not enough, mixture or inversion of venous and arterial blood in the CFP would occur, and heat generation at the solenoid was very severe. To solve these problems, a third model was designed in the current study. To increase pump output, hydrodynamic analysis was performed. The SV was divided into inlet and outlet to control the blood mixture or inversion. To suppress heat generation, each SV was driven back and forth by two solenoids, one on each side of the SV. The model revealed satisfactory results in a mock circulatory system.

Biomedical Engineering↗

Pulsatile blood flow asymmetry in paired human legs.

Average leg blood flow has been extensively measured using non-invasive methods, but knowledge concerning pulsatile flow at specific leg cross-sections in normal or vascularly impaired limbs is quite limited. The present study used nuclear magnetic resonance flowmetry to address two fundamental questions; (1) to what extent are pulsatile flow differences present between paired-legs? and (2) is paired-leg flow symmetry affected by the presence of lower extremity arterial disease (LEAD)? Comparisons of left-right leg pulsatile blood flow (ml/min), perfusion (ml/min/100cc), and arterial status index at multiple leg sites showed highly significant correlations between legs (P < 0.001) in 57 normal and 37 patients with LEAD. To evaluate symmetry, the ratio of lower to higher paired-leg flow parameter values at five below-knee sites were averaged. Results showed all ratios significantly greater in normal subjects (P < 0.001). These findings establish the distribution and range of leg flow symmetry in vascularly normal individuals and show significant symmetry reductions accompanying bilateral LEAD. Although the cause of the asymmetry is presently unknown, non-uniform disease progression between paired legs may be involved. These initial findings provide a basis for subsequent research regarding the possible use of bilateral flow asymmetry assessment to further clarify the pathophysiological progression process and the possibility of using symmetry-based parameters to develop early markers of sub-clinical peripheral arterial disease progression.

Adult↗

In vitro targeting of acoustically reflective immunoliposomes to fibrin under various flow conditions.

We have previously demonstrated the development of acoustically reflective liposomes as a novel ultrasound contrast agent, that can be conjugated to antibodies for site specific acoustic enhancement of pathologically altered vascular tissue. The liposomes are echogenic due to the lipid composition, without gas entrapment, and have a size of less than one micron (Alkan-Onyuksel et al., 1996). When conjugated to anti-fibrinogen antibodies, the liposomes have the ability to attach to fibrin coated surfaces and thrombi in vitro as demonstrated by scanning electron microscopy and ultrasound imaging (Demos et al., 1997a). Anti-fibrinogen liposomes were shown to attach to fibrous atheroma and thrombi in a Yucatan miniswine model of induced atherosclerosis whereas liposomes conjugated to anti-intercellular adhesion molecule-1 (anti-ICAM-1) were demonstrated to target early stage atherosclerotic plaques (Demos et al., 1997b). The purpose of this study is to evaluate the binding characteristics of anti-fibrinogen liposomes in vitro under a variety of flow conditions in order to optimize the targeting ability of the immunoliposomes. Radiolabeled anti-fibrinogen liposomes were applied to fibrin coated filter paper and placed in a flow circuit under controlled flow conditions. Flow conditions were altered to study the effects of different shear stresses, temperature, plasma flow and pulsatile flow on the retention of liposomes to fibrin after set time periods. The retention of liposomes conjugated to polyclonal and monoclonal antibodies as well as Fab fragments made from monoclonal antibodies were compared. The binding characteristics of liposomes conjugated to different quantities of polyclonal antibodies were analyzed. At physiological shear stress of 1.5 N/m2 (15 dynes/cm2) over 70% of the liposomes remained attached to fibrin after two hours. A smaller and greater portion of the liposomes remained attached at higher and lower shear stresses respectively. Plasma components and temperature had no effect on liposomal retention whereas pulsatile flow resulted in a slight reduction in binding. Monoclonal antibodies showed a slight trend of reduced retention to fibrin over time as compared with polyclonal antibodies and Fab fragments. The quantity of antibody conjugated to the liposomes plays a role in liposome retention as demonstrated by the reduction in liposome retention caused by reducing the quantity of antibody conjugated to the liposomes. Anti-fibrinogen liposomes were retained to the fibrin surface to a large extent under all flow conditions likely to occur in vivo and therefore can provide site specific ultrasound contrast for a long enough time period to allow for imaging after injection.

Acoustics↗