Biomedical subjects

J M Tarbell

Publications and source records attributed to J M Tarbell.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of VEGF on retinal microvascular endothelial hydraulic conductivity: the role of NO.

PURPOSE: Vascular endothelial growth factor (VEGF) increases microvascular permeability in vivo and has been hypothesized to play a role in plasma leakage in diabetic retinopathy. Few controlled studies have been conducted to determine the mechanism underlying the effect of VEGF on transport properties (e.g., hydraulic conductivity [Lp]). This study was conducted to determine the effect of VEGF on bovine retinal microvascular endothelial LP and the role of nitric oxide (NO) and the guanylate cyclase/guanosine 3', 5'-cyclic monophosphate/protein kinase G (GC/cGMP/PKG) pathway downstream of NO in mediating the VEGF response. METHODS: Bovine retinal microvascular endothelial cells (BRECs) were grown on porous polycarbonate filters, and water flux across BREC monolayers in response to a pressure differential was measured to determine endothelial LP RESULTS: VEGF (100 ng/ml) increased endothelial LP: within 30 minutes of addition and by 13.8-fold at the end of 3 hours of exposure. VEGF stimulated endothelial monolayers to release NO and incubation of the BRECs with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 100 microM) significantly attenuated the VEGF-induced LP increase. It was observed that incubation of the monolayers with the GC inhibitor LY-83583 (10 microM) did not alter the VEGF-mediated LP: response. Addition of the cGMP analogue 8-br-cGMP (1 mM) did not change the baseline LP over 4 hours. Also, the PKG inhibitor KT5823 (1 microM) did not inhibit the response of BREC LP to VEGF. CONCLUSIONS: These experiments indicate that VEGF elevates hydraulic conductivity in BRECs through a signaling mechanism that involves NO but not the GC/cGMP/PKG pathway.

Alkaloids↗

PubMed1999

Effect of pressure on hydraulic conductivity of endothelial monolayers: role of endothelial cleft shear stress.

Significant changes in transvascular pressure occur in pulmonary hypertension, microgravity, and many other physiological and pathophysiological circumstances. Using bovine aortic endothelial cells grown on porous, rigid supports, we demonstrate that step changes in transmural pressure of 10, 20, and 30 cmH(2)O induce significant elevations in endothelial hydraulic conductivity (L(p)) that require 5 h to reach new steady-state levels. The increases in L(p) can be reversed by addition of a stable cAMP analog (dibutyryl cAMP), and the increases in L(p) in response to pressure can be inhibited significantly with nitric oxide synthase inhibitors (N(G)-monomethyl-L-arginine and nitro-L-arginine methyl ester). The increase in L(p) was not due to pressure-induced stretch because the endothelial cell (EC) support was rigid. It is unlikely that the increase in L(p) was due to a direct effect of pressure because exposure of the cells to elevated pressure (25 cmH(2)O) for 4 h had no effect on the volume flux driven by a transmural pressure of 10 cmH(2)O. We hypothesize that elevated endothelial cleft shear stress induced by elevated transmural flow in response to elevated pressure stimulates the increase in L(p) through a nitric oxide-cAMP-dependent mechanism. This is consistent with recent studies of the effects of shear stress on the luminal surface of ECs. We provide simple estimates of endothelial cleft shear stress, which suggest magnitudes comparable to those imposed by blood flow on the luminal surface of ECs.

Animals↗

PubMed1999

In vitro studies of gas bubble formation by mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Recent clinical research using transcranial Doppler ultrasonography has shown the presence of emboli in the cranial circulation of some mechanical heart valve patients. Due to the high-intensity signals produced by these emboli, it has been suggested that they are small gas bubbles. Meanwhile, transesophageal echocardiography of mechanical heart valve patients has shown images of bright, mobile particles (also considered to be gas bubbles) near the valve. Motivated by these reports, a series of in vitro studies was performed to investigate the relationship between dissolved gas concentration and the incidence of bubble formation after valve closure. METHODS: A mock circulatory loop was used to study a Medtronic Hall tilting disc valve in the mitral position of the Penn State Electrical Ventricular Assist Device (EVAD). The valve was videotaped as it operated in saline with various levels of dissolved CO2. A Doppler ultrasound probe served as a bubble detector on the outflow side of the EVAD. Measurements of vaporous cavitation intensity with a high-fidelity pressure transducer were also made. Similar experiments were then performed in porcine blood, using an imaging ultrasound transducer to detect bubbles. RESULTS: Bubbles were seen moving off the valve in the retrograde direction just after closure. The ultrasound probe detected these bubbles downstream, indicating a bubble lifetime on the order of seconds. It was observed with high-speed video that bubble formation and cavitation are separate events and occur at different times during valve closure. Bubbles were more likely to be observed when CO2 levels were higher. Experiments in blood provided images of bubbles near the valve, predominantly at higher CO2 levels and high valve loading conditions. CONCLUSIONS: These results show that stable gas bubbles can form during mechanical heart valve operation. The bubbles likely form from the combined effects of gaseous nuclei formed by cavitation, low-pressure regions associated with regurgitant flow, and the presence of CO2, a highly soluble gas.

Animals↗

PubMed1998

Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group.

Blood-retinal barrier (BRB) breakdown is a hallmark of diabetic retinopathy, but the molecular changes that cause this pathology are unclear. Occludin is a transmembrane component of interendothelial tight junctions that may regulate permeability at the BRB. In this study, we examined the effects of vascular endothelial growth factor (VEGF) and diabetes on vascular occludin content and barrier function. Sprague-Dawley rats were made diabetic by intravenous streptozotocin injection, and age-matched animals served as controls. After 3 months, BRB permeability was quantified by intravenous injection of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), Mr 66 kDa, and 10-kDa rhodamine-dextran (R-D), followed by digital image analysis of retinal sections. Retinal fluorescence intensity for FITC-BSA increased 62% (P < or = 0.05), but R-D fluorescence did not change significantly. Occludin localization at interendothelial junctions was confirmed by immunofluorescence, and relative protein content was determined by immunoblotting of retinal homogenates. Retinal occludin content decreased approximately 35% (P < or = 0.03) in the diabetic versus the control animals, whereas the glucose transporter GLUT1 content was unchanged in rat retinas. Additionally, treatment of bovine retinal endothelial cells in culture with 0.12 nmol/l or 12 nmol/l VEGF for 6 h reduced occludin content 46 and 54%, respectively. These data show that diabetes selectively reduces retinal occludin protein expression and increases BRB permeability. Our findings suggest that the elevated VEGF in the vitreous of patients with diabetic retinopathy increases vascular permeability by downregulating occludin content. Decreased tight junction protein expression may be an important means by which diabetes causes increased vascular permeability and contributes to macular edema.

Animals↗

PubMed1998

A comparison of the cavitation potential of prosthetic heart valves based on valve closing dynamics.

BACKGROUND AND AIMS OF THE STUDY: This study compares the cavitation potential of prosthetic heart valves based on valve closing dynamics. METHODS: A laser sweeping technique measured valve closing dynamics (average closing velocity and deceleration) immediately before valve closure. A high-fidelity, piezoelectric pressure transducer was mounted proximal to the mitral valve and measured the high-frequency pressure fluctuations caused by cavitation bubble formation and collapse after valve closure. The band-pass filtered root mean squared (RMS) value of the mitral pressure signal was used as a measure of cavitation intensity. The combination of these two techniques allowed the direct correlation of valve dynamics and cavitation intensity for each valve closure. The effects of three parameters on prosthetic heart valve dynamics and cavitation were examined: valve geometry (Medtronic Hall and Björk-Shiley Monostrut), occluder material (pyrolytic carbon and Delrin), and gap width between the occluder and housing. A dimensional analysis was also performed to investigate the general form of the relationship between valve dynamics and cavitation intensity. RESULTS: For all of the valves investigated in this study, the RMS pressure increased (signifying an increase in cavitation) as the average closing velocity and deceleration increased. In order to compare the cavitation potential of the valves, the RMS pressure was estimated at specific closing velocities using the linear regression of RMS pressure versus average closing velocity for each valve. The effects of valve geometry, occluder material and gap width were then examined at high valve loading conditions (closing velocity of 4.0 m/s). For both pyrolytic carbon and Delrin, the Medtronic Hall valves had significantly higher RMS pressures than did the Björk-Shiley Monostrut valves. For a given valve geometry, the pyrolytic carbon occluder had a significantly higher RMS pressure than the Delrin occluder. The valve gap width did not have a significant effect on RMS pressure. The dimensional analysis revealed the general relationship among average closing velocity, occluder material properties and cavitation intensity. CONCLUSIONS: The results presented here contribute to our fundamental understanding of cavitation on mechanical heart valves.

Heart Valve Prosthesis↗

PubMed1997

Physiological transport properties of cultured retinal microvascular endothelial cell monolayers.

PURPOSE: To characterize baseline transport properties: hydraulic conductivity (Lp), albumin permeability (Pe), and transendothelial electrical resistance (TER) of bovine retinal microvascular endothelial cells (RMEC) in the development of an in vitro model of the blood-retinal barrier (BRB). METHODS: RMEC were grown on porous, polycarbonate filters for determination of the number of days required to achieve minimal transport rates. Lp, Pe, and TER were measured by utilizing a bubble tracking spectrophotometer, by quantifying the diffusional movement of fluorescein isothiocyanate-labeled albumin, and by utilizing a Millipore electrical resistance meter, respectively. RESULTS: Lp decreased significantly from 7.82 +/- 0.85 x 10(-7) (mean +/- SEM) cm/sec/cm H2O at post-plating Day 5 to 1.44 +/- 0.26 x 10(-7) cm/sec/cm H2O at Day 9. Pe of the monolayer also decreased progressively with days post-plating from 3.44 +/- 0.53 x 10(-6) cm/sec at Day 7 to a minimum of 1.95 +/- 0.29 x 10(-6) cm/sec at Day II. Peak TER fluctuated until Day 7, when it began to steadily increase from 17.14 ohm-cm2 to a peak value of 25.42 ohm-cm2 at Day 10, decreasing from then on to 22.24 ohm.cm2 on Day 12. Known disrupters of the BRB, NECA and VEGF, elicited significant increase in RMEC Lp showing the sensitivity of this model to pharmacological alterations. CONCLUSIONS: Our data indicate that RMEC grown on polycarbonate filters form a restrictive monolayer of cells, which exhibit dynamic alterations in response to pharmacological agents, thus demonstrating an in vitro model of the BRB. Future studies with the model may offer insights into the pathogenesis of retinal vascular diseases and allow convenient testing of pharmacological interventions.

Adenosine↗

PubMed1997

Effects of tilting disk heart valve gap width on regurgitant flow through an artificial heart mitral valve.

While many investigators have measured the turbulent stresses associated with forward flow through tilting disk heart valves, only recently has attention been given to the regurgitant jets formed as fluid is squeezed through the gap between the occluder and housing of a closed valve. The objective of this investigation was to determine the effect of gap width on the turbulent stresses of the regurgitant jets through a Björk-Shiley monostrut tilting disk heart valve seated in the mitral position of a Penn State artificial heart. A 2 component laser-Doppler velocimetry system with a temporal resolution of 1 ms was used to measure the instantaneous velocities in the regurgitant jets in the major and minor orifices around the mitral valve. The gap width was controlled through temperature variation by taking advantage of the large difference between the thermal expansion coefficients of the Delrin occluder and the Stellite housing of Björk-Shiley monostrut valves. The turbulent shear stress and mean (ensemble averaged) velocity were incorporated into a model of red blood cell damage to assess the potential for hemolytic damage at each gap width investigated. The results revealed that the minor orifice tends to form stronger jets during regurgitant flow than the major orifice, indicating that the gap width is not uniform around the circumference of the valve. Based on the results of a red blood cell damage model, the hemolytic potential of the mitral valve decreases as the gap width increases. This investigation also established that the hemolytic potential of the regurgitant phase of valve operation is comparable to, if not greater than, the hemolytic potential of forward flow, consistent with experimental data on hemolysis.

Blood Flow Velocity↗

PubMed1997

Wall shear rate distribution in an abdominal aortic bifurcation model: effects of vessel compliance and phase angle between pressure and flow waveforms.

The goal of this study was to determine how vessel compliance (wall motion) and the phase angle between pressure and flow waves (impedance phase angle) affect the wall shear rate distribution in an atherogenic bifurcation geometry under sinusoidal flow conditions. Both rigid and elastic models replicating the human abdominal aortic bifurcation were fabricated and the wall shear rate distribution in the median plane of the bifurcation was determined using the photochronic flow visualization method. In the elastic model, three phase angle conditions were simulated (+12, -17, -61 deg), and the results compared with those obtained in a similar rigid model. The study indicates a very low (magnitude close to zero) and oscillatory wall shear rate zone within 1.5 cm distal to the curvature site on the outer (lateral) wall. In this low shear rate zone, unsteadiness (pulsatility) of the flow greatly reduces the mean (time-averaged) wall shear rate level. Vessel wall motion reduces the wall shear rate amplitude (time-varying component) up to 46 percent depending on the location and phase angle in the model. The mean wall shear rate is less influenced by the wall motion, but is reduced significantly in the low shear region (within 1.5 cm distal to the curvature site on the outer wall), thus rendering the wall shear rate waveform more oscillatory and making the site appear more atherogenic. The effect of the phase angle is most noteworthy on the inner wall close to the flow divider tip where the mean and amplitude of wall shear rate are 31 and 23 percent lower, respectively, at the phase angle of -17 deg than at -61 deg. However, the characteristics of the wall shear rate distribution in the low shear rate zone on the outer wall that are believed to influence localization of atherosclerotic disease, such as the mean wall shear rate level, oscillation in the wall shear rate waveform, and the length of the low and oscillatory wall shear rate zone, are similar for the three phase angles considered. The study also showed a large spatial variation of the phase angle between the wall shear stress waveform and the circumferential stress waveform (hoop stress due to radial artery expansion in response to pressure variations) near the bifurcation (up to 70 deg). The two stresses became more out of phase in the low mean shear rate zone on the outer wall (wall shear stress wave leading hoop stress wave as much as 125 deg at the pressure-flow phase angle of -61 deg) and were significantly influenced by the impedance phase angle.

Aorta, Abdominal↗

PubMed1997

Numerical simulation of mass transfer in porous media of blood vessel walls.

The tunica media of a blood vessel wall is modeled as a heterogeneous medium composed of a periodic array of cylindrical smooth muscle cells and a continuous interstitial fluid phase of proteoglycan and collagen fibers. By applying Brinkman's model to describe the behavior of the interstitial flow, we obtain an analytical solution for the transmural flow field through the periodic array of smooth muscle cells in the form of a power series, making it possible to compute the convection of solutes in the interstitial phase. With reaction of solutes at the surface of smooth muscle cell membranes being treated as boundary conditions and the diffusion of species being limited to the interstitial fluid phase only, mass transfer in the media of blood vessel walls is simulated numerically using Cray supercomputers. It is found that the Sherwood number (the dimensionless mass-transfer coefficient) is not only constant for all interior smooth muscle cells but also minimally sensitive to changes of parameters controlling the relative rates of diffusion and convection in the interstitial fluid phase and the reaction on the smooth muscle cell surface. In addition, the Sherwood number is not very sensitive to changes in the volume fraction of smooth muscle cells. A homogeneous, one-dimensional model (effective-medium model) is also developed to predict the bulk concentration profile in the media, based on the equivalent properties of the effective medium derived from the heterogeneous medium. A comparison of results from the one-dimensional model and two-dimensional simulation is quite satisfactory for all practical ranges of parameters. It is also determined that, for a small molecule such as ATP, the mass transfer to the surface of smooth muscle cells is "reaction limited" as assumed previously in the literature, whereas, for a large molecule such as low-density lipoprotein, the mass transfer might not be reaction limited.

Animals↗

PubMed1996

Shear stress-induced release of PGE2 and PGI2 by vascular smooth muscle cells.

This study addresses the direct effect of fluid flow shear stress on production of the vascular mediators, PGE2 and PGI2 by vascular smooth muscle cells (SMC). Results indicate that shear stress increases PGE2 and PGI2 release in SMC. The production patterns, however, differ between PGE2 and PGI2. For PGE2, the rate of production is moderate for the first three hours after the onset of shear stress, then dramatically increases between the fourth and fifth hours, returning to basal levels in the sixth hour. On the other hand, the rate for PGI2 production is maximal right after the onset of shear and remains elevated for the first three hours. The rate then plateaus and remains at a moderate level during the next three hours. The results also indicate that SMC production of PGI2 is more sensitive to shear stress than PGE2 production since a level of 0.5 dynes/cm2 produces a maximal PGI2 release whereas 1 dyne/cm2 produces only 1/4 the response seen at 20 dynes/cm2 for PGE2. The physiological implications of fluid shear stress regulation of SMC are discussed.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Compliance and diameter mismatch affect the wall shear rate distribution near an end-to-end anastomosis.

The development of intimal hyperplasia near the anastomosis of a vascular graft to an artery may be related to changes in the wall shear rate distribution. Mismatches in compliance and diameter at the end-to-end anastomosis of a compliant artery and a rigid graft cause shear rate disturbances that may induce intimal hyperplasia and ultimately graft failure. The goal of this study is to determine how compliance mismatch, diameter mismatch, and impedance phase angle affect the wall shear rate distribution in end-to-end anastomosis models under sinusoidal flow conditions. Wall shear rates are obtained through flow visualization using a photochromic dye. In a model with a well-matched graft diameter (6% undersized), the compliance mismatch causes low mean wall shear rates near the distal anastomosis. Considering diameter mismatch, the wall shear rate distributions in 6% undersized, 16% undersized, and 13% oversized graft models are markedly different at similar phase angles. In the two undersized graft models, the minimum mean shear rate occurs near the distal anastomosis, and this minimum is lower in the model with greater diameter mismatch. The oversized graft model has a minimum mean shear rate near the proximal anastomosis. Thus in all three models, the minimum mean wall shear rate is observed at the site of the divergent geometry. The impedance phase angle, which can be altered by disease states and vasoactive drugs, has a minor effect on the wall shear rate amplitude far from the anastomosis but a more pronounced effect closer to the anastomosis. Mean wall shear rates under sinusoidal flow conditions are significantly lower than under steady flow conditions at the same mean flow rate, but they are fairly insensitive to phase angle changes. In order to avoid the divergent geometry that may cause lower wall shear rates, we recommend that compliance mismatch be minimized whenever possible and that graft diameter be chosen to match the arterial diameter at the relevant physiologic pressure, not at the reduced pressure present when the graft is implanted.

Anastomosis, Surgical↗

PubMed1996

Influence of non-Newtonian behavior of blood on flow in an elastic artery model.

Two different non-Newtonian models for blood, one a simple power law model exhibiting shear thinning viscosity, and another a generalized Maxwell model displaying both shear thinning viscosity and oscillatory flow viscoelasticity, were used along with a Newtonian model to simulate sinusoidal flow of blood in rigid and elastic straight arteries. When the spring elements were removed from the viscoelastic model resulting in a purely viscous shear thinning fluid, the predictions of flow rate and WSS were virtually unaltered. Hence, elasticity of blood does not appear to influence its flow behavior under physiological conditions in large arteries, and a purely viscous shear thinning model should be quite realistic for simulating blood flow under these conditions. When a power law model with a high shear rate Newtonian cutoff was used for sinusoidal flow simulation in elastic arteries, the mean and amplitude of the flow rate were found to be lower for a power law fluid compared to a Newtonian fluid experiencing the same pressure gradient. The wall shear stress was found to be relatively insensitive to fluid rheology but strongly dependent on vessel wall motion for flows driven by the same pressure gradient. The effect of wall motion on wall shear stress could be greatly reduced by matching flow rate rather than pressure gradient. For physiological flow simulation in the aorta, an increase in mean WSS but a reduction in peak WSS were observed for the power law model compared to a Newtonian fluid model for a matched flow rate waveform.

Aorta, Thoracic↗

PubMed1996

Mitral heart valve cavitation in an artificial heart environment.

BACKGROUND AND AIMS OF THE STUDY: The formation and subsequent collapse of vaporous cavities in the fluid around mechanical heart valves at valve closure can create stresses large enough to damage both the valve itself and blood cells. Improved understanding of cavitation mechanisms should lead to a reduction in the cavitation potential of future valve designs. MATERIALS AND METHODS: This study compares eight mechanical mitral valves of two different geometries (Monostrut and Medtronic Hall), occluder housing gaps (tight, medium, and leaky), and occluder materials (Delrin and pyrolytic carbon). The valves were evaluated in a model ventricle of the Penn State Electric Ventricular Assist Device (EVAD) operating within a mock circulatory loop. The EVAD represents one half of a total artificial heart. The mock loop consisted of silicone tubing connected to elements designed to mimic the compliant and resistant properties of the natural circulation. Cavitation was controlled by varying the degree of filling of the ventricle: low filling caused higher valve closing velocities resulting in greater cavitation intensities than complete filling of the ventricle. The intensity of cavitation was quantified using a parameter derived from the high frequency fluctuations in the mitral pressure that occur around the valve during cavitation events. The shape of the cavitation pressure signature and that of the power spectrum of the cavitation pressure signature were used in addition to the cavitation intensity parameter to make comparisons between valves. RESULTS: Of the three valve characteristics studied, occluder material showed the most significant influence on cavitation intensity: valves with pyrolytic carbon occluders demonstrated greater cavitation than did those with Delrin discs. CONCLUSION: It is hypothesized that the dominant form of cavitation on the valves studied is related to vortex formation and that occluder material influences the intensity of cavitation through the strength of the tension wave generated at valve closure, while geometry and gap have only secondary effects. Future studies are planned to incorporate this technique in an in vivo environment.

Biophysical Phenomena↗

PubMed1995

Nonlinear analysis of oscillatory flow, with a nonzero mean, in an elastic tube (artery).

Oscillatory flow of a Newtonian fluid in an elastic tube, which is a model of blood flow in arteries, is analyzed in this paper. For a rigid tube, the steady flow field can be described by Poiseuille's law and the unsteady flow field by Womersley's solution. These are the linearized solutions for flow in elastic tubes. To evaluate the importance of nonlinear effects, a perturbation solution is developed realizing that the amplitude of arterial wall movement is small (typically 5-10 percent of the diameter). The nonlinear effects on the amplitude of the wall shear rate, on the amplitude of the pressure gradient, and on the mean velocity profile have been considered. Nonlinear effects on the oscillatory components depend on Womersley's unsteadiness parameter (alpha), the ratio between the mean and amplitude of the flow rate, the diameter variation, and the phase difference between the diameter variation and the flow rate (phi) which is indicative of the degree of wave reflection. On the other hand, the mean velocity profile is found to be dependent on the steady-streaming Reynolds number, Rs. When Rs is small, the mean velocity profile is parabolic (1-xi 2); however, when Rs is large, the velocity profile is distorted by the nonlinear effect and can be described by sin (pi xi 2). The increase of the amplitude and reduction of the mean of wall shear rate as phi changes from 0 to -90 deg suggests an indirect mechanism for the role of hypertension in arterial disease: hypertension-->increased wave reflection-->wall shear stress is reduced and more oscillatory.

Arteries↗

PubMed1995

Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells.

The arterial media is modeled as a periodic array of cylindrical smooth muscle cells residing in a matrix comprised of proteoglycan and collagen fibers. Using Brinkman's model to describe transmural flow through such a fibrous media, we calculate the effective hydraulic permeability of the media and the wall shear stress on smooth muscle cells. Two interesting results are obtained: first, the wall shear stress on smooth muscle cells is on the order of 1 dyne/cm2, which is the range known to affect endothelial cells in vitro; second, the flow resistance due to smooth muscle cells is not negligible compared to the resistance due to the fiber matrix.

Arteries↗

PubMed1995

Shear stress increases hydraulic conductivity of cultured endothelial monolayers.

To examine the effect of shear stress on hydraulic conductivity (Lp) of bovine aortic endothelial cell monolayers grown on polycarbonate filters, we developed a rotating disk system, which imposed a defined shear stress while Lp was measured. A 10-cmH2O pressure differential was applied to monolayers, and baseline Lp was established between 1.65 +/- 0.85 and 4.94 +/- 1.05 x 10(-7) cm.s-1.cmH2O-1. One-hour exposure to 10 dyn/cm2 shear stress caused a significant (P < 0.05) increase in Lp by 2.16-fold (+/- 0.42), and Lp remained elevated when shear stress was removed. Three-hour exposure to shear stresses between 0.1 and 20.0 dyn/cm2 revealed a threshold for shear-induced increase in Lp of 0.5 dyn/cm2. At 20 dyn/cm2, Lp initially decreased by 30% (+/- 13.4%, P < 0.05) and then increased to a level 3.76-fold (+/- 0.83, P < 0.05) greater than baseline Lp at 3 h. The shear-induced increase in Lp was reversed with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM) and could be significantly (P < 0.05) inhibited when monolayers were preincubated with 0.3 mM DBcAMP, a concentration that did not significantly affect baseline Lp. Furthermore, preincubation with a general phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (1 mM), completely blocked the shear-induced increase in Lp. On the basis of these results, we conclude that shear stress alters endothelial Lp through a cellular mechanism involving signal transduction, not by a purely physical mechanism.

1-Methyl-3-isobutylxanthine↗

PubMed1994

A study of the wall shear rate distribution near the end-to-end anastomosis of a rigid graft and a compliant artery.

The development of intimal hyperplasia in the anastomotic region of a vascular graft which does not match the compliance of the parent artery may be related to altered wall shear rates near the anastomosis. The purpose of this study is to determine the effect of radial wall motion and the phase angle between pressure and flow waves (impedance phase angle) on the wall shear rate distribution near an end-to-end vascular graft anastomosis model incorporating a rigid graft and a compliant artery. The wall shear rate is determined from near-wall velocity profiles obtained by a flow visualization method using a photo-chromic dye for different locations near the anastomosis. The results show that the mean wall shear rate under pulsatile flow conditions is 15-30% lower than under steady flow conditions at the same mean flow rate. The effect of the impedance phase angle on the mean wall shear rate is shown to be small, but its effect on the amplitude of the wall shear rate is not negligible. For our anastomosis model which has well-matched diameters at the mean pressure, the mean shear rates at the distal sites are lower than at the proximal sites by 15-23%. We suppose that the differences in the mean wall shear rate between the proximal and distal sites are related to the convergent/divergent geometry caused by the mismatch of the compliance. Since the distal side of the anastomosis is more prone to intimal hyperplasia, lower shear rates near the distal anastomosis favor the hypothesis that low/oscillatory wall shear rates lead to intimal hyperplasia.

Anastomosis, Surgical↗

PubMed1994

Numerical simulation of unsteady laminar flow through a tilting disk heart valve: prediction of vortex shedding.

Heart valves induce flow disturbances which play a role in blood cell activation and damage, but questions of the magnitude and spatial distribution of fluid stresses (wall shear stress and turbulent stress) cannot be readily addressed with current experimental techniques. Therefore, a numerical simulation procedure for flow through artificial heart valves is presented. The algorithm employed is based on the Navier-Stokes equations in generalized curvilinear coordinates with artificial compressibility for coupling of velocity and pressure. The algorithm applies a finite-difference technique on a body-conforming composite grid around the heart valve disk on which the numerical simulations are performed. Steady laminar flow over a backward-facing step and unsteady laminar flow inside a square driven cavity are computed to validate the algorithm. Two-dimensional, time-accurate simulation of flow through a tilting disk valve with a steady upstream Reynolds number as high as 1000 reveals the complex behavior of 'vortex shedding'. By scaling the results at the Reynolds number of 1000 to peak systolic flow conditions, the maximum value of shear stress on the valve disk is estimated to be 770 dyn cm-2. The 'apparent' Reynolds stress associated with vortex shedding is estimated to be as high as 3900 dyn cm-2 with a vortex shedding frequency of about 26 Hz. The 'apparent' Reynolds stress value is of similar magnitude as reported in experiments but would not be expected to damage blood cells because the spatial scales associated with vortex shedding are much larger than blood cell dimensions.

Algorithms↗