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D N Ku

Publications and source records attributed to D N Ku.

At least 55 records · Page 3Linked to original sources

Flow patterns in the abdominal aorta under simulated postprandial and exercise conditions: an experimental study.

Specific hemodynamic factors have been shown to be associated with atherosclerotic plaque localization at the human carotid bifurcation. Flow field characteristics may also determine plaque distribution in the abdominal aorta. We therefore characterized flow patterns in a glass model abdominal aorta that included its major branches under conditions of steady flow. Outflow resistances of the celiac, superior mesenteric, renal, inferior mesenteric, and iliac arteries were varied to produce flow distributions consistent with rest, the postprandial state, and vigorous lower limb exercise. Flow patterns were visualized with three colors of dye injected simultaneously through capillary tubes at selected locations and recorded as still photographs and by cinephotography on videotapes. Under resting conditions a large region of flow separation and stagnation occurred at the posterior wall of the aorta directly opposite the orifices of the superior and inferior mesenteric arteries. Similar separation regions were observed during the simulated postprandial state but diminished markedly when distal outflow was increased to levels consistent with exercise. In the highly susceptible infrarenal aortic segment, beginning about 2 cm below the renal artery orifices, multiple secondary flow patterns with three to four counterrotating vortex formations were observed under both resting and postprandial conditions but disappeared in the exercise state. Secondary flow patterns were not noted in the suprarenal abdominal aorta, which is usually relatively spared. Such features have been related to plaque localization elsewhere, and the disappearance of these patterns with increased flow velocity during exercise is consistent with the previously noted protective effect of unidirectional laminar high-flow states. The beneficial effects of physical fitness programs may be related in part to these hemodynamic modifications.

Aorta, Abdominal↗

Optimal graft diameter: effect of wall shear stress on vascular healing.

Arterial walls tend to adapt to maintain a specific wall shear stress. The formation of neointimal hyperplasia and endothelial cell healing of polytetrafluoroethylene grafts may also be governed by wall shear stress, which suggests that an optimal graft diameter may exist. To test this, 40 polytetrafluoroethylene grafts with internal diameters of 3, 6, and 8 mm were inserted end to end in the femoral and carotid arteries of 10 mongrel dogs. Total flow and diameter were measured, and grafts were stained with Evans blue dye, fixed by pressure perfusion, and analyzed by computer for anastomotic neointimal thickening, graft pseudointimal thickening, and degree of endothelial coverage. Mean calculated shear stress was 41 dyne/cm2 for the 3 mm grafts, 7 dyne/cm2 for the 6 mm grafts, and 3 dyne/cm2 for the 8 mm grafts. Fifteen weeks later the patency rate was 0 of 10 for the 3 mm grafts, 16 of 20 for the 6 mm grafts, and 7 of 10 for the 8 mm grafts. The mean graft shear stress was calculated to be 10 dyne/cm2 for the 6 mm grafts and 4 dyne/cm2 for the 8 mm grafts. Pseudointima lining the graft was composed of disorganized protein and cell remnants. The rough surface contained no overlying endothelium. Anastomotic neointima contained a layer of well-organized smooth muscle cells covered by a single layer of polygonal-shaped endothelial cells. A transition zone of thrombus, which is sandwiched by a wedge of smooth muscle cells near the graft surface and covered by endothelial cells, is described. Mean thickness of pseudointima of the patent 8 mm grafts was 150 microns thicker than that of the 6 mm grafts. Anastomotic neointimal thickness was 110 microns thicker in the 8 mm grafts compared with the 6 mm grafts. Among the 6 mm grafts, the carotid grafts had an average initial shear stress of 10 dyne/cm2, whereas the femoral grafts averaged a lower 5 dyne/cm2 and yielded pseudointima and neointima that were 40 microns thicker. The percent graft surface area covered with neointima did not differ among the grafts of differing diameter either proximally or distally. Lower shear stresses produced greater amounts of pseudointimal thickening within polytetrafluoroethylene grafts and neointimal thickening at their anastomoses. Conversely, the high shear stress from small-diameter grafts was associated with poor graft patency. These results suggest that an optimal graft diameter may help to prevent neointimal hyperplasia and graft thrombosis.

Animals↗

Reverse flow in the major infrarenal vessels--a capacitive phenomenon.

The arterial blood flow waveform is shown to change abruptly when passing from the thoracic aorta into the abdominal aorta in humans. Although this change has been accurately predicted by numerical solution of complicated pulse propagation equations, this paper demonstrates the ability of a simple lumped parameter model to explain this change in the waveforms using easily understood physical terms. The model correctly predicts changes in flow waveform under conditions of exercise and peripheral vascular disease. This analysis is useful in understanding abdominal artery physiology and explains the basis for clinical ultrasound Doppler examination of the legs.

Aorta, Abdominal↗

Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries.

Atherosclerosis affects the major elastic and muscular arteries, but some vessels are largely spared while others may be markedly diseased. The carotid bifurcation, the coronary arteries, the infrarenal abdominal aorta, and the vessels supplying the lower extremities are at highest risk. The propensity for plaque formation at bifurcations, branchings, and curvatures has led to conjectures that local mechanical factors such as wall shear stress and mural tensile stress potentiate atherogenesis. Recent studies of the human vessels at high risk, and of corresponding models, have provided quantitative evidence that plaques tend to occur where flow velocity and shear stress are reduced and flow departs from a laminar, unidirectional pattern. Such flow characteristics tend to increase the residence time of circulating particles in susceptible regions while particles are cleared rapidly from regions of relatively high wall shear stress and laminar unidirectional flow. The flow patterns associated with plaque localization are most prominent during systole. Long-term consequences are therefore likely to be greatly enhanced by elevated heart rate and may exert a selective effect on the coronary arteries. The point-by-point redistribution of wall tension at regions of geometric transition has not been quantitatively related to plaque localization. Enlargement of arteries as plaques increase in size and the associated modeling of plaque and wall configuration tend to preserve an adequate and regular lumen cross section. Hemodynamic forces appear to determine changes in vessel diameter so as to restore normal levels of wall shear stress, while wall thickness architecture, and composition are closely related to tensile stress. Hemodynamic forces may also be implicated in the symptom-producing destabilization of plaques, especially in relation to wall instabilities near stenoses. The relative roles of wall shear stress, tensile stress, and the metabolism of the artery wall in the progression and complication of atherosclerosis remain to be clarified. Development of clinical techniques for relating hemodynamic and tensile properties to plaque location, stenosis, and composition should permit pathologists to provide new insights into the bases for the topographic and individual differences in plaque progression and outcome.

Adaptation, Physiological↗

Laser Doppler anemometer measurements of pulsatile flow in a model carotid bifurcation.

Hemodynamics at the human carotid bifurcation is important to the understanding of atherosclerotic plaque initiation and progression as well as to the diagnosis of clinically important disease. Laser Doppler anemometry was performed in a large scale model of an average human carotid. Pulsatile waveforms and physiologic flow divisions were incorporated. Disturbance levels and shear stresses were computed from ensemble averages of the velocity waveform measurements. Flow in the common carotid was laminar and symmetric. Flow patterns in the sinus, however, were complex and varied considerably during the cycle. Strong helical patterns and outer wall flow separation waxed and waned during each systole. The changing flow patterns resulted in an oscillatory shear stress at the outer wall ranging from -13 to 9 dyn cm-2 during systole with a time-averaged mean of only -0.5 dyn cm-2. This contrasts markedly with an inner wall shear stress range of 17-50, (mean 26) dyn cm-2. The region of transient separation was confined to the carotid sinus outer wall with no reverse velocities detected in the distal internal carotid. Notable disturbance velocities were also time-dependent, occurring only during the deceleration phase of systole and the beginning of diastole. The present pulsatile flow studies have aided in identifying hemodynamic conditions which correlate with early intimal thickening and predict the physiologic level of flow disturbances in the bulb of undiseased internal carotid arteries.

Blood Flow Velocity↗

Shear stress regulation of artery lumen diameter in experimental atherogenesis.

We studied the adaptive response of the arterial wall and intimal thickening under conditions of increased flow in an atherogenic model. Blood flow was increased by construction of an arteriovenous fistula between the right iliac artery and vein in six cynomolgus monkeys fed a diet containing 2% cholesterol and 25% peanut oil. The left iliac artery served as the control. Serum cholesterol increased from 135 +/- 22 mg/dl to 880 +/- 129 mg/dl during the experiment. After 6 months, blood flow in the right iliac artery (420 +/- 95 ml/min) was 10 times greater than in the left iliac artery (44 +/- 9 ml/min, p less than 0.005). Flow velocity in the right iliac artery (31 +/- 6 cm/sec) was more than twofold greater than in the left (12 +/- 1 cm/sec, p less than 0.05). Despite the marked difference in blood flow and flow velocity, calculated wall shear stress was the same in both the right (16 +/- 4 dynes/cm2) and left iliac vessels (15 +/- 2 dynes/cm2) because of a twofold increase in lumen diameter (p less than 0.001) of the right iliac artery. Shear stress in the aorta was also normal (12 +/- 2 dynes/cm2). There was no difference in plaque deposition or mean intimal thickness between the right and left iliac arteries. In the right iliac artery there was a twofold increase in media cross-sectional area (p less than 0.001) but no change in media thickness or total wall thickness. Tangential wall tension and tangential wall stress were two times greater on the right than on the left (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The contribution of valves to saphenous vein graft resistance.

Saphenous vein resistance influences graft flow rates and may affect graft patency in lower limb revascularization. To quantitate specifically the contribution of saphenous vein valves to this resistance, 10 human saphenous veins (mean length 68 cm, diameter 0.42 mm, and 5.2 valves per vein) were perfused with water under carefully controlled pressure gradients designed to simulate different peripheral resistances in the outflow bed. The Reynolds number was maintained at 350 to 600, within the physiologic range for in vivo grafts. Veins were perfused under both venous (10 mm Hg) and arterial (100 mm Hg) mean pressures to determine the effects of distension on the overall resistance of the conduit. The valves were bisected according to Leather's techniques and flow was measured in both directions, antegrade (simulating "reversed" grafts) and retrograde (simulating "in situ" grafts). Data (mean +/- standard error) were normalized to the baseline flow for each vein with intact valves and expressed as a percentage change. Data were analyzed by means of Student's t test (p less than 0.05). Baseline antegrade flow with intact valves averaged 71.0 +/- 3.0 ml/min at pressure gradients (delta P) of 10 mm Hg and 95.0 +/- 2.6 ml/min for delta P = 20 mm Hg. After valve incision, antegrade flow (reversed) increased an average of 29% at both pressure gradients. Retrograde flow (in situ) through the bisected valves was only 19% greater than baseline antegrade flow and was significantly less than antegrade flow through bisected valves. The difference is explained by theoretic considerations of stenosis area and orifice shape. The increases in flow did not correlate with vein length or diameter, nor did flow change with different distension pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessel Prosthesis↗

The effects of non-Newtonian viscoelasticity and wall elasticity on flow at a 90 degrees bifurcation.

To study the fundamentals of hemodynamics in arteries, the flow parameters: pulsatility, elasticity and non-Newtonian viscoelasticity were considered in detail in a 90 degrees-T-bifurcation of a rigid and elastic model. The velocity distribution 2.5 mm behind the bifurcation in the straight tube was measured with a laser-Doppler-anemometer. The fluid used was an aqueous glycerine solution and a viscoelastic Separan mixture. Flow visualization studies were done with a sheet of laser light in the plane of the bifurcation. The velocity distribution was measured for both steady and pulsatile flows with a laser-Doppler-anemometer in a backward scattered way. From the velocity measurements the shear gradients were calculated. Substantial differences were found in the flow behavior of Newtonian and non-Newtonian fluids, especially behind the bifurcation in the main tube, where secondary flows and flow separation started. Also, differences due to the elastic and rigid wall could be seen. Very high shear gradients were found in the flow between main flow and the separation zone which can lead to a damage of the blood cells.

Arteries↗

Scleral creep in vitro resulting from cyclic pressure pulses: applications to myopia.

In the axially myopic eyeball, the posterior hemisphere is distended and the sclera is thinner in this region. One hypothetical mechanism is that high intraocular pressures cause an irreversible stretching of this region. For irreversible stretching to occur, the sclera must be stressed beyond the elastic limit. This paper presents a biaxial stress-strain curve for rabbit sclera and defines a plastic yield point. Experimental evidence is presented which demonstrates that cyclic pulses of high intraocular pressure can cause irreversible deformation. A mathematical equation is developed which successfully predicts creep rate (i.e., deformation rate) of an eye subjected to short duration pulses of high intraocular pressure. This relation holds for frequencies of cyclic pressures which vary over two orders of magnitude, and over a wide range of temperatures and pressures.

Animals↗

Extractive alkylation of 5,2'-dichloro-4'-nitrosalicylanilide (niclosamide) for gas-liquid chromatographic analysis.

Niclosamide (5,2'-dichloro-4'-nitrosalicylanilide), formulated as the ethanolamine salt, is one of the most effective and widely used molluscicides for the control of snail vectors of schistosomiasis, a parasitic disease afflicting over 200 million people in more than 70 countries. This report details the development of a sensitive, specific analytical method for the evaluation of niclosamide formulations and assessment of the impact of residues on the environment. Efficient (greater than 85%) phase-transfer, N,O-dimethylation of niclosamide and the synthesized 5-deschloro analog internal standard, followed by gas-liquid chromatographic separation and electron-capture detection, permits the determination of as little as 10 ppb analyte in fortified, stagnant water. Tetrabutylammonium chloride was the phase-transfer agent, while methyl iodide was the methylating agent of choice among four investigated.

Animals↗

Effects of acceleration on the accuracy of MR phase velocity measurements.

Acceleration in blood flow can affect the accuracy of phase velocity measurements. Convective acceleration is due to changes in flow geometry and is independent of the time-varying acceleration caused by flow pulsatility. To analyze the effects of convective acceleration on flow velocity measurements, phase velocity measurements were obtained in steady laminar flow in the convergent segment of a 90%, hourglass-shaped stenosis phantom at a Reynolds number of 1,500. Measurements at the stenosis indicated that convective acceleration caused the measured values of average cross-sectional velocity to deviate as much as 37% from the theoretical values. The magnitude of the error could be accounted for by including the convective acceleration term in the phase shift equation. Convective acceleration effects should not be ignored in flow velocity measurements through stenoses, even when time-dependent acceleration due to flow pulsatility can be neglected.

Acceleration↗

Determination of wall shear stress in the aorta with the use of MR phase velocity mapping.

MR phase velocity mapping was used to calculate wall shear stress (WSS) in the suprarenal and infrarenal abdominal aorta, two sites with very different proclivities for development of a atherosclerosis. For the eight subjects studied, the average value of the mean (time averaged over the cardiac cycle) WSS in the suprarenal aorta was 10.4 dynes/cm2 at the posterior wall and 8.6 at the anterior wall. In the infrarenal aorta, WSS values were 4.7 at the posterior wall and 6.1 at the anterior wall. Peak WSS over the cardiac cycle was 48 and 54 at the anterior and posterior walls of the suprarenal aorta, respectively, and 33 and 30 at the anterior and posterior walls of the infrarenal aorta, respectively. Wide variation was found in both mean and peak WSS values among subjects. However, for 28 of 32 locations examined, mean and peak WSS were higher in the suprarenal aorta than in the infrarenal aorta. Because atherosclerosis is more likely to form in the infrarenal aorta than in the suprarenal aorta, this study supports the hypothesis that low WSS is a localizing factor for atherosclerosis, and high WSS may act as a deterrent against formation of atherosclerosis.

Adult↗

Comparison of phantom and computer-simulated MR images of flow in a convergent geometry: implications for improved two-dimensional MR angiography.

The signal loss that occurs in regions of disturbed flow significantly decreases the clinical usefulness of MR angiography in the imaging of diseased arteries. This signal loss is most often attributed to turbulent flow; but on a typical MR angiogram, the signal is lost in the nonturbulent upstream region of the stenosis as well as in the turbulent downstream region. In the current study we used a flow phantom with a forward-facing step geometry to model the upstream region. The flow upstream of the step was convergent, which created high levels of convective acceleration. This region of the flow field contributes to signal loss at the constriction, leading to overestimation of the area of stenosis reduction. A computer program was designed to simulate the image artifacts that would be caused by this geometry in two-dimensional time-of-flight MR angiography. Simulated images were compared with actual phantom images and the flow artifacts were highly correlated. The computer simulation was then used to test the effects of different orders of motion compensation and of fewer pixels per diameter, as would be present in MR angiograms of small arteries. The results indicated that the computational simulation of flow artifacts upstream of the stenosis provides an important tool in the design of optimal imaging sequences for the reduction of signal loss.

Arteriosclerosis↗

Computer modeling of the abdominal aorta using magnetic resonance images.

An approach is described for creating a 3-D computer model of the abdominal aorta from just two projective images. The aorta is modeled by conical segments connecting circular cross sections. Accuracy of this technique is within 1 mm. From the 3-D computer model, quantitative measurements of vessel diameter, length, and position are available for any subset of the arterial structure. Visualization is enhanced by displaying the computer model rather than a direct set of images obtained from different perspectives. Ambiguities from overlapping branches can be resolved by rotating the model or by eliminating the interfering structures. This approach has been applied in both phantom studies, in which quantitative comparisons were made, and in vivo studies, in which qualitative evaluations were made.

Aorta, Abdominal↗

Flow in T-bifurcations: effect of the sharpness of the flow divider.

The local geometry of a bifurcation has been hypothesized to be a potential geometrical risk factor for the development of atherosclerosis. While flow division and branch area ratios clearly affect the flow field, the importance of the flow divider shape is not as clear. A fast spectral element computational fluid mechanics (CFD) solver was used to simulate flow through 90 degrees T-bifurcations with three different flow divider shapes. Other factors, such as flow partition, area ratio, and bifurcation angle, were kept constant. A Reynolds number range of 15 to 350 was studied to bracket experimental results in the literature. The variation in the sharpness of the corners had a dramatic effect on both the flow field and wall shear stress distribution in the side branch, but little effect on the flow in the main tube. The magnitude of reverse velocities and wall shear stress in the side branch increased linearly over a physiological range of Reynolds number and corner shape. This paper verifies the accuracy and usefulness of spectral element CFD in studying three-dimensional hemodynamics.

Arteriosclerosis↗

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↗

A novel method for efficient drug delivery.

Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded systemically or which exhibit very short half-lives in vivo. In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow system. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Qinf>0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Qinf<0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.

Antithrombins↗