Biomedical subjects

John M Tarbell

Publications and source records attributed to John M Tarbell.

At least 19 recordsLinked to original sources

PubMed2006

Oxygen mass transport in a compliant carotid bifurcation model.

The purpose of the present study was to investigate oxygen mass transfer in the human carotid bifurcation, focusing on the effects of the wall compliance and flow field on the temporal variation and spatial distribution of the oxygen wall flux. Details of unsteady convective-diffusive oxygen transport were examined numerically using a compliant model of the human carotid bifurcation and realistic blood flow waveforms. Results reveal that axial flow separation at the outer common-internal carotid wall can significantly alter the flow field, oxygen tension field, and oxygen wall flux distribution. At the outer wall of the sinus, the Sherwood number, Sh (non-dimensional oxygen wall flux), takes on significantly lower values than at other sites due to the attenuation of transport rates by convective flow away from wall. More specifically, the lowest value of Sh was Sh approximately 6 (in the sinus), which is much lower than the value of the non-dimensional oxygen consumption rate (Damkohler number, Da) in the reactive wall tissue (Da=29-39). At the inner wall of the sinus, Sh approximately 170 is far above the expected value of Da. This implies that flow separation on the outer wall of the sinus provides a very strong fluid mechanical barrier to oxygen transport; whereas at the inner wall of the sinus, the mechanism of transport is controlled by the wall consumption rate.

Algorithms↗

PubMed2006

Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium: correlation of asynchronous hemodynamics and pathology in vivo.

Coronary arteries are the most disease prone arteries in the circulation and are characterized by unique hemodynamic features, wherein wall shear stress (WSS) induced by blood flow and circumferential strain (CS) driven by pressure are highly out-of-phase temporally (asynchronous hemodynamics). To investigate whether there is a correlation between asynchronous hemodynamics and pathology in vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries (left anterior descending artery cLAD), and aorta (aortic arch inner curvature, outer curvature, and straight descending aorta). En face imaging showed strong similarities in EC nuclear length:width ratio and angle of orientation in the cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had significantly reduced (>5-fold) eNOS mRNA levels compared to all aortic regions, while ET-1 showed an opposite trend ( approximately 2.5-fold). Coronary arteries with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and ET-1 gene expression profiles while the EC nuclei morphology did not differ from non-atherogenic regions in the aorta. This study demonstrates a correlation between asynchronous hemodynamics and pro-atherogenic gene expression patterns in vivo that is induced by hemodynamics inherent to the circulation.

Animals↗

PubMed2006

Large Negative Stress Phase Angle (SPA) attenuates nitric oxide production in bovine aortic endothelial cells.

Hemodynamics plays an important role in cardiovascular physiology and pathology. Pulsatile flow (Q), pressure (P), and diameter (D) waveforms exert wall shear stress (WSS), normal stress, and circumferential strain (CS) on blood vessels. Most in vitro studies to date have focused on either WSS or CS but not their interaction. Recently, we have shown that concomitant WSS and CS affect EC biochemical response modulated by the temporal phase angle between WSS and CS (stress phase angle, SPA). Large negative SPA has been shown to occur in regions of the circulation where atherosclerosis and intimal hyperplasia are prevalent. Here, we report that nitric oxide (NO) biochemical secretion was significantly decreased in response to a large negative SPA of -180 deg with respect to an SPA of 0 degrees in bovine aortic endothelial cells (BAEC) at 5 h. A new hemodynamic simulator for the study of the physiologic SPA was used to provide the hemodynamic conditions of pro-atherogenic (SPA = -180 deg) and normopathic (SPA = 0 deg) states. The role of complex hemodynamics in vascular remodeling, homeostasis, and pathogenesis can be advanced by further assessment of the hypothesis that a large negative SPA is pro-atherogenic.

Animals↗

PubMed2005

Regulation of hydraulic conductivity in response to sustained changes in pressure.

The present study addresses the effect of a sustained change in pressure on microvascular permeability assessed by hydraulic conductivity (Lp) measurements from microvessels of the rat mesentery. With a microperfusion technique, transvascular filtration (normalized to surface area; Jv/S) and Lp were measured in small arterioles (baseline Lp= 0.26 x 10(-7) cm.s(-1).cmH2O(-1)) and venules (baseline Lp= 2.88 x 10(-7) cm.s(-1).cmH2O(-1)). The main finding of this study is that step increases in microvascular pressure led to time-dependent alterations of L(p). Immediately after a twofold step increase in pressure, Jv/S increased in proportion to the pressure change. This observation is consistent with Starling's law that predicts filtration proportional to the overall pressure gradient when Lp is constant. However, when Jv/S measurements continued for 60-90 min past the step in pressure, there was an initial decrease in Jv/S for 30 min ("sealing effect") followed by a substantial increase in Jv/S out to 90 min. The sustained increase in Jv/S suggests an increase in Lp of 36 +/- 7% for small arterioles and 42 +/- 5% for small venules (P < 0.05 for both). In addition, the increase in Lp in response to an increase in pressure was attenuated significantly by nitric oxide synthase inhibition. These results indicate that a pressure-induced mechanical stimulus (possibly Jv) activates a NO-dependent biochemical response that leads to an increase in hydraulic conductivity.

Adaptation, Physiological↗

PubMed2005

Regulation of capillary hydraulic conductivity in response to an acute change in shear.

The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity (L(p)) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Transvascular fluid filtration rate in the branching vessel was measured with a Landis technique. Flow (shear)-induced increases in L(p) disappeared within 20-30 s of the removal of the shear and could be eliminated with nitric oxide synthase inhibition. The shear-induced increase in L(p) was greater in capillaries compared with terminal arterioles. An acute change in shear may regulate L(p) by a nitric oxide-dependent mechanism that displays heterogeneity within a microvascular network.

Algorithms↗

PubMed2005

Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity.

Vascular smooth muscle cell (SMC) migration is a hallmark of intimal hyperplasia (IH), the progression of which is affected by hemodynamic conditions at the diseased site. The realization that SMCs are exposed to blood flow in both denuded vessels (direct blood flow) and intact vessels (interstitial blood flow) motivated this study of the effects of fluid flow shear stress (SS) on SMC migration. Rat aortic SMCs were seeded onto Matrigel-coated cell culture inserts, and their migratory activity toward PDGF-BB when exposed to SS in a rotating disk apparatus was quantified. Four hours of either 10 or 20 dyn/cm2 SS significantly inhibited SMC migration to the bottom side of the insert. This inhibition was associated with downregulation of SMC matrix metalloproteinase (MMP)-2 activation. Four hours of 10 dyn/cm2 SS also drastically increased SMC production of NO. A NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester; 100 microM) abolished the shear-induced increase in SMC NO production as well as the inhibition of migration and MMP-2 activity. A NO donor (S-nitroso-N-acetyl-penicillamine; 500 microM) suppressed SMC migration via the reduction of both total and active MMP-2 levels. Addition of 10 microM MMP-2 inhibitor I to inserts significantly reduced SMC migration. Western blots showed no effect of 4 h of 20 dyn/cm2 SS on SMC production of PDGF-AA, another chemical known to suppress SMC migration. Thus it appears that SS acts to suppress SMC migration by upregulating the cellular production of NO, which in turn inhibits MMP-2 activity.

Animals↗

PubMed2005

Shear stress regulates HUVEC hydraulic conductivity by occludin phosphorylation.

Human umbilical vein endothelial cells (HUVECs) display hydraulic conductivity (L(P)) responses to shear stress that differ markedly from the responses of bovine aortic endothelial cells (BAECs). In HUVECs, 5, 10, and 20 dyn cm(-2) steady shear stress transiently increased L(P) with a return to preshear baseline after a 2-h exposure to shear stress. Pure oscillatory shear stress of 0 +/- 20 dyn cm(-2) (mean+/-amplitude) had no effect on L(P), whereas superposition of oscillatory shear stress on steady shear stress suppressed the effect induced by steady shear stress alone. Shear reversal (amplitude greater than mean) was not necessary for the inhibitory influence of oscillatory shear stress. The transient increase of L(P) by steady shear stress was not affected by incubation with BAPTA-AM (10 microM), suggesting calcium independence of the shear response. Decreasing nitric oxide (NO) concentration with L-NMMA (100 microM), a nitric oxide synthase (NOS) inhibitor, did not inhibit the HUVEC L(P) response to shear stress. At the protein level, 10 dyn cm(-2) shear stress did not affect the total content of occludin, but it did elevate the phosphorylation level transiently. The positive correlation between occludin phosphorylation and hydraulic conductivity parallels observations in BAECs and suggests that occludin phosphorylation may be a general mediator of shear-L(P) responses in diverse endothelial cell types.

Animals↗

PubMed2005

Cellular fluid mechanics and mechanotransduction.

Mechanotransduction, the transformation of an applied mechanical force into a cellular biomolecular response, is briefly reviewed focusing on fluid shear stress and endothelial cells. Particular emphasis is placed on recent studies of the surface proteoglycan layer (glycocalyx) as a primary sensor of fluid shear stress that can transmit force to apical structures such as the plasma membrane or the actin cortical web where transduction can take place or to more remote regions of the cell such as intercellular junctions and basal adhesion plaques where transduction can also occur. All of these possibilities are reviewed from an integrated perspective.

Actin Cytoskeleton↗

PubMed2005

Acoustic and visual characteristics of cavitation induced by mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: A sudden pressure drop and recovery can induce cavitation in liquids. Mechanical heart valves (MHVs) generate such a pressure drop at closure, and cavitation generation around MHVs has been demonstrated many times. Cavitation is suspected as being a cause of blood and valve material damage. METHODS: In this in-vitro experiment, visual images and acoustic signals associated with MHV cavitation were studied to reveal cavitation characteristics. Björk-Shiley Convex-Concave valves, one with a pyrolytic carbon occluder and one with a Delrin occluder, were installed in a single-shot valve chamber. Cavitation intensity was controlled by load (dP/dt) and air content of water. The acoustic signal was measured using a hydrophone and visual images recorded with a high-speed digital camera system. RESULTS: Cavitation images showed that 10 ppm water rarely developed cavitation, unlike the 16 ppm water. A distinct peak pressure was observed at cavitation collapse that was a good indicator of MHV cavitation intensity. The average of the peak pressures revealed that cavitation intensity increased faster with increasing load for the 16 ppm water. CONCLUSION: The use of the peak pressure may be the preferred method for correlating cavitation intensity in structures for which the separation of valve closure noise and cavitation signal is difficult, as for the valves studied here.

Acoustics↗

PubMed2005

The effect of dissolved carbon dioxide on cavitation intensity in mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Mechanical heart valves (MHVs) are known to induce cavitation during closure and rebound. Cavitation may lead to blood element damage and stable bubble formation, with the latter introducing emboli into the cranial circulation and increasing the risk of stroke. Previous research has suggested that CO2 is the primary blood gas involved in stable bubble growth, due to its high solubility compared to that of oxygen or nitrogen. The primary objective of this study is to determine the role that CO2 plays in MHV-induced cavitation bubble formation. METHODS: Degassed water (5 ppm) was supplemented with CO2 at partial pressures of 0, 40 and 100 mmHg. Cavitation was visualized using high-speed videography for 29 mm Björk-Shiley Monostrut and Medtronic Hall MHVs in the mitral position. Experimental parameters (heart rate, systolic duration, and left ventricular pressure) were adjusted to provide dp/dt values of 500, 2,500 and 4,500 mmHg/s. High-frequency pressure fluctuations of cavitation bubble collapse were detected using a hydrophone. RESULTS: Root-mean square (RMS) values were calculated to quantify the cavitation intensity for both MHVs at the three loading conditions. The images of cavitation bubble formation and collapse were correlated to their respective RMS values. This study revealed no statistical difference between the cavitation intensities produced by either of the MHVs for the range of CO2-supplemented degassed water tested. For example, at the most physiologic loading condition of 2,500 mmHg/s, the RMS values for the Björk-Shiley Monostrut valve in degassed water containing 0 and 100 mmHg CO2 were 32.7 +/- 3.5 and 34.3 +/- 6.1 mmHg, respectively. CONCLUSION: The results of this in-vitro study show that, despite affecting stable bubble growth, the presence and quantity of dissolved CO2 does not affect the intensity of the cavitation events occurring during impact of the valve occluder with its housing. Therefore, the role of CO2 is limited to stable bubble development.

Carbon Dioxide↗

PubMed2004

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a "bumper-car" model.

We propose a conceptual model for the cytoskeletal organization of endothelial cells (ECs) based on a major dichotomy in structure and function at basal and apical aspects of the cells. Intracellular distributions of filamentous actin (F-actin), vinculin, paxillin, ZO-1, and Cx43 were analyzed from confocal micrographs of rat fat-pad ECs after 5 h of shear stress. With intact glycocalyx, there was severe disruption of the dense peripheral actin bands (DPABs) and migration of vinculin to cell borders under a uniform shear stress (10.5 dyne/cm2; 1 dyne = 10 microN). This behavior was augmented in corner flow regions of the flow chamber where high shear stress gradients were present. In striking contrast, no such reorganization was observed if the glycocalyx was compromised. These results are explained in terms of a "bumper-car" model, in which the actin cortical web and DPAB are only loosely connected to basal attachment sites, allowing for two distinct cellular signaling pathways in response to fluid shear stress, one transmitted by glycocalyx core proteins as a torque that acts on the actin cortical web (ACW) and DPAB, and the other emanating from focal adhesions and stress fibers at the basal and apical membranes of the cell.

Actins↗

PubMed2004

Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells.

OBJECTIVE: Endothelium-derived vasoactive agents NO, endothelin-1 (ET-1), and prostacyclin (PGI2) not only regulate vascular tone but also influence atherogenic processes, including smooth muscle migration and proliferation, as well as monocyte and platelet adhesion. Complex hemodynamics characterized by the temporal phase angle between mechanical factors circumferential strain and wall shear stress (stress phase angle [SPA]) have been implicated in regions prone to pathologic development, such as atherosclerosis and intimal hyperplasia, in coronary and peripheral arteries where the mechanical forces are highly asynchronous (SPA=-180 degrees ). We determined the gene expression of endothelial NO synthase (eNOS), ET-1, and cyclooxygenase-2 (COX-2) affected by asynchronous hemodynamics (SPA=-180 degrees ) relative to normal hemodynamics (SPA=0 degrees ) in bovine aortic endothelial cells. METHODS AND RESULTS: Quantitative competitive RT-PCR analysis showed that eNOS production (at 5 and 12 hours) and COX-2 production (at 5 hours) were reduced at the gene expression level by asynchronous hemodynamics (SPA=-180 degrees) compared with synchronous hemodynamics (SPA=0 degrees ), whereas ET-1 exhibited an opposite trend (at 5 and 12 hours). NO, ET-1, and PGI2 secretion followed their respective gene expression profiles after 5 and 12 hours. CONCLUSIONS: Together, these data suggest that highly asynchronous mechanical force patterns (SPA=-180 degrees ) can elicit proatherogenic vasoactive responses in endothelial cells at the gene expression level, indicating a novel mechanism that induces cardiovascular pathology.

Animals↗

PubMed2004

Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response.

This study addressed the influence of the rate of shear stress application on aortic smooth muscle cell (SMC) contraction and the role of specific glycosaminoglycans in this mechanotransduction. Rat aortic SMCs were exposed to either a step increase in shear stress (0 to 25 dyn/cm(2)) or a ramp increase in shear stress (0 to 25 dyn/cm(2) over 5 min) in a parallel plate flow chamber, and cell contraction was characterized by cell area reduction. SMCs contracted at levels similar to those reported previously and equally in response to both a step and ramp increase in shear stress. When the cells were pretreated with heparinase III or chondroitinase ABC to remove the glycosaminoglycans heparan sulfate and chondroitin sulfate, respectively, from the glycocalyx, the contraction response to increases in shear stress was significantly inhibited. These studies indicate that specific components of the SMC glycocalyx play an important role in the mechanotransduction of shear stress into a contractile response and that the rate of application of shear stress does not affect the SMC contraction.

Adaptation, Physiological↗

PubMed2004

Internal elastic lamina affects the distribution of macromolecules in the arterial wall: a computational study.

The internal elastic lamina (IEL), which separates the arterial intima from the media, affects macromolecular transport across the medial layer. In the present study, we have developed a two-dimensional numerical simulation model to resolve the influence of the IEL on convective-diffusive transport of macromolecules in the media. The model considers interstitial flow in the medial layer that has a complex entrance condition because of the presence of leaky fenestral pores in the IEL. The IEL was modeled as an impermeable barrier to both water and solute except for the fenestral pores that were assumed to be uniformly distributed over the IEL. The media were modeled as a heterogeneous medium composed of an array of smooth muscle cells (SMCs) embedded in a continuous porous medium representing the interstitial proteoglycan and collagen fiber matrix. Results for ATP and low-density lipoprotein (LDL) demonstrate a range of interesting features of molecular transport and uptake in the media that are determined by considering the balance among convection, diffusion, and SMC surface reaction. The ATP concentration distribution depends strongly on the IEL pore structure because ATP fluid-phase transport is dominated by diffusion emanating from the fenestral pores. On the other hand, LDL fluid-phase transport is only weakly dependent on the IEL pore structure because convection spreads LDL laterally over very short distances in the media. In addition, we observe that transport of LDL to SMC surfaces is likely to be limited by the fluid phase (surface concentration less than bulk concentration), whereas ATP transport is limited by reaction on the SMC surface (surface concentration equals bulk concentration).

Adenosine Triphosphate↗

PubMed2004

Rat aortic smooth muscle cells contract in response to serum and its components in a calcium independent manner.

Diluted serum provides a model of interstitial fluid that can be used to study the response of smooth muscle cells (SMCs) to interstitial flow. The effect of serum and some of its components on SMC contraction (area reduction) and intracellular calcium ([Ca2+]i) response were characterized in rat aortic SMC in vitro. Rat aortic SMCs contracted dramatically to fetal bovine serum (FBS), bovine serum albumin (BSA), and lysophosphatidic acid (LPA) within 5 min of exposure. By 30 min, cell areas were significantly reduced. Even at concentrations as low as 0.0005% FBS, 0.004% BSA and 0.25 microM LPA, cell areas were significantly different from controls at 30 min. The [Ca2+]i response was significant for serum and LPA at these low concentration levels, but BSA did not elicit a significant [Ca2+]i response at concentrations of 0.1% or lower. Under calcium controlled conditions in which SMCs were pretreated with 10 microM BAPTA-AM, contraction levels were not statistically different from non-calcium controlled conditions even when SMCs were exposed to the highest concentration of serum, BSA, or LPA. It appears that LPA and albumin are components of interstitial fluid that contribute to SMC contraction through calcium-independent mechanisms.

Animals↗

PubMed2004

Control of the arteriolar myogenic response by transvascular fluid filtration.

Mechanisms of the myogenic response have not been completely established. We hypothesized that transvascular fluid filtration from plasma across smooth muscle cells (SMC) and into the surrounding interstitium helps regulate arteriolar myogenic tone. Arteriolar diameters in the rat mesentery were monitored before and following vascular occlusion with a glass micropipette. Arteriolar occlusion not only gave an increase in hydrostatic pressure that initiated myogenic constriction upstream of the pipette, but also allowed measurement of fluid filtration rate by monitoring the movement of vascular red blood cells. A statistically significant correlation (P < 0.001) existed between basal myogenic tone and fluid filtration. Additionally, the myogenic response was attenuated by 47% +/- 7% (N = 10) when an osmotic solution of albumin or albumin plus Ficoll was infused into the bloodstream to decrease fluid filtration by 53% +/- 3%. Moreover, the same inhibition of myogenic tone was found in isolated, cannulated rat soleus muscle arterioles when filtration was osmotically attenuated by intravascular dextran. Taken together, these results are consistent with the hypothesis that shear stress on arteriolar smooth muscle, induced by transvascular fluid filtration, is a contributing factor that helps control myogenic tone.

Animals↗

PubMed2004

VEGF increases paracellular transport without altering the solvent-drag reflection coefficient.

Vascular endothelial growth factor (VEGF) increases microvascular permeability and has been implicated in the development of numerous pathologies including diabetic retinopathy (DR), hypoxia/ischemia, and tumor biology. The transport pathways by which water and solutes cross the endothelium in response to VEGF, however, are not completely understood. We measured, in real time, bovine retinal endothelial cell (BREC) hydraulic conductivity (Lp), 70 kDa dextran permeability (Pe), and the solvent-drag reflection coefficient (sigma) before and after addition of 50 ng/ml VEGF. The diffusional permeability coefficient for dextran (Pd) was measured before pressure gradient application. The sudden application of a 10-cm H2O hydrostatic pressure gradient induced water and solute fluxes that decayed to steady-state values after approximately 2 h. Subsequently, the addition of VEGF significantly increased Lp and Pe by 4.3-fold +/- 0.7-fold and 3.0-fold +/- 0.3-fold, respectively, after 110 min; however, the reflection coefficient remained approximately constant throughout the experiment (approximately 0.8). These observations suggest that water and dextran utilize common paracellular channels across BREC monolayers. Furthermore, the addition of VEGF increases the number or availability of channels but does not alter the selectivity of the monolayer to 70 kDa dextran.

Animals↗

PubMed2004

Wall shear-rate estimation within the 50cc Penn State artificial heart using particle image velocimetry.

Particle image velocimetry (PIV) has been gaining acceptance as a routine tool to evaluate the flow fields associated with fluid mechanical devices. We have developed algorithms to investigate the wall shear-rates within the 50cc Penn State artificial heart using low magnification, conventional particle image velocimetry (PIV). Wall shear has been implicated in clot formation, a major post-implant problem with artificial hearts. To address the issues of wall scattering and incomplete measurement volumes, associated with near wall measurements, we have introduced a zero masking and a fluid centroid shifting technique. Simulations using different velocity fields were conducted with the techniques to assess their viability. Subsequently, the techniques were applied to the experimental data collected. The results indicate that the size of the interrogation region should be chosen to be as small as possible to maximize resolution while large enough to ensure an adequate number of particles per region. In the current study, a 16 x 16 interrogation window performed well with good spatial resolution and particle density for the estimation of wall shear rate. The techniques developed with PIV allow wall shear-rate estimates to be obtained from a large number of sites at one time. Because a planar image of a flow field can be determined relatively rapidly, PIV may prove useful in any preliminary design procedure.

Algorithms↗