Flow-dependent Changes Research Articles

Nasal High-Flow (NHF) Improves Ventilation in Patients with Interstitial Lung Disease (ILD)-A Physiological Study.

Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO2. Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and-to illustrate the effects-nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. NHF leads to a reduction in paCO2. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients.

Novel multivariate quantile mapping methods for ensemble post-processing of medium-range forecasts

Statistical post-processing is an indispensable tool for providing accurate weather forecasts and early warnings for weather extremes. Most statistical post-processing is univariate, with dependencies introduced via use of an empirical copula. Standard empirical methods take a dependence template from either the raw ensemble output (ensemble copula coupling, ECC) or the observations (Schaake Shuffle, SSh). There are drawbacks to both methods. In ECC it is assumed that the raw ensemble simulates the dependence well, which is not always the case (e.g. 2-meter temperature in The Netherlands). The Schaake Shuffle is not able to capture flow dependent changes to the dependence and the choice of observations is key. Here we compare a reshuffled standard ensemble model output statistics (EMOS) approach with two multivariate bias adjustment approaches that have not been used before in a post-processing context: 1) the multivariate bias correction with N-dimensional probability density function transform (MBCn) and 2) multivariate ranks that are defined with optimal assignment (OA). These methods have the advantage that they are able to explicitly capture the dependence structure that is present in the observations. We apply ECC, the Schaake Shuffle, MBCn and OA to 2-m and dew point temperature forecasts at seven stations in The Netherlands. Forecasts are verified with both univariate and multivariate methods, and using a heat index derived from both variables, the wet-bulb globe temperature (WBGT). Our results demonstrate that the spatial and inter-variable dependence structure is more realistic in MBCn and OA compared to ECC or the Schaake Shuffle. The variogram score shows that while ECC is most skilful for the first two days, at moderate lead times MBCn is most skilful and at the longest lead times OA is more skilful than both ECC and MBCn. Overall, we highlight the importance of considering the dependence between variables and locations in the statistical post-processing of weather forecasts.

Clinical application of stress echocardiography for valvular heart disease.

Stress echocardiography is widely used to assess several cardiovascular diseases, including ischemic heart disease, valvular heart disease (VHD), heart failure, congenital heart disease, and pulmonary hypertension. In valvular heart disease with asymptomatic severe or symptomatic non-severe status, stress echocardiography plays a central role in the management. As of 2017, the updated American College of Cardiology/American Heart Association and European Society of Cardiology/European Association for Cardio-Thoracic Surgery VHD guidelines recommended stress testing to (1) confirm symptoms and (2) evaluate the hemodynamic response to exercise. In patients with undetermined VHD severity in the presence of low-flow status, it can also be helpful to determine whether the VHD is severe based on flow-dependent changes in response to stress. The clinical indications of stress echocardiography in VHD have expanded with growing evidence for prognosis and being an early marker for interventions. As a result, demand has increased in major cardiology societies for the standardization of stress echocardiography in VHD. Echocardiographic centers should be aware of the clinical potential of stress echocardiography to ensure its optimal application and performance in VHD. This article reviews the clinical application of stress echocardiography, including dobutamine, semisupine bicycle, treadmill, and leg-positive pressure for VHD patient management, and focuses on the current consensus regarding the use of stress echocardiography in VHD. Stress echocardiography is safe and should be encouraged, especially in heart valve clinics, to understand the complex mechanism in asymptomatic patients.

Bioreactance is a reliable method for estimating cardiac output at rest and during exercise

Bioreactance is a novel noninvasive method for cardiac output measurement that involves analysis of blood flow-dependent changes in phase shifts of electrical currents applied across the thorax. The present study evaluated the test-retest reliability of bioreactance for assessing haemodynamic variables at rest and during exercise. 22 healthy subjects (26 (4) yrs) performed an incremental cycle ergometer exercise protocol relative to their individual power output at maximal O2 consumption (Wmax) on two separate occasions (trials 1 and 2). Participants cycled for five 3 min stages at 20, 40, 60, 80 and 90% Wmax. Haemodynamic and cardiorespiratory variables were assessed at rest and continuously during the exercise protocol. Cardiac output was not significantly different between trials at rest (P=0.948), or between trials at any stage of the exercise protocol (all P>0.30). There was a strong relationship between cardiac output estimates between the trials (ICC=0.95, P<0.001) and oxygen consumption (ICC=0.99, P<0.001). Stroke volume was also not significantly different between trials at rest (P=0.989) or during exercise (all P>0.15), and strong relationships between trials were found (ICC=0.83, P<0.001). The bioreactance method demonstrates good test-retest reliability for estimating cardiac output at rest and during different stages of graded exercise testing including maximal exertion.

Time and flow-dependent changes in the p27kip1 gene network drive maladaptive vascular remodeling

Although clinical studies have identified that a single nucleotide polymorphism in the p27(kip1) gene is associated with success or failure after vein bypass grafting, the underlying mechanisms for this difference are not well defined. Using a high-throughput approach in a flow-dependent vein graft model, we explored the differences in p27(kip1)-related genes that drive the enhanced hyperplastic response under low-flow conditions. Bilateral rabbit carotid artery interposition grafts with jugular vein were placed with a unilateral distal outflow branch ligation to create differential flow states. Grafts were harvested at 2 hours and at 1, 3, 7, 14, and 28 days after implantation, measured for neointimal area, and assayed for cell proliferation. Whole-vessel messenger RNA was isolated and analyzed using an Affymetrix (Santa Clara, Calif) gene array platform. Ingenuity Pathway Analysis (Ingenuity, Redwood City, Calif) was used to identify the gene networks surrounding p27(kip1). This gene set was then analyzed for temporal expression changes after graft placement and for differential expression in the alternate flow conditions. Outflow branch ligation resulted in an eightfold difference in mean flow rates throughout the 28-day perfusion period (P < .001). Flow reduction led to a robust hyperplastic response, resulting in a significant increase in intimal area by 7 days (0.13 ± 0.04 mm(2) vs 0.014 ± 0.006 mm(2); P < .005) and progressive growth to 28 days (1.37 ± 0.05 mm(2) vs 0.39 ± 0.06 mm(2); P < .001). At 7 days, low-flow grafts demonstrated a burst of actively dividing intimal cells (36.4 ± 9.4 cells/mm(2) vs 11.5 ± 1.9 cells/mm(2); P = .04). Sixty-five unique genes within the microarray were identified as components of the p27(kip1) network. At a false discovery rate of 0.05, 26 genes demonstrated significant temporal changes, and two dominant patterns of expression were identified. Class comparison analysis identified differential expression of 11 genes at 2 hours and seven genes and 14 days between the high-flow and low-flow grafts (P < .05). At 2 hours, oncostatin M and cadherin 1 were the most differentially expressed. Cadherin 1 and protein kinase B exhibited the greatest differential expression at 14 days. Alterations in flow and shear stress result in divergent patterns of vein graft remodeling. Associated with the dramatic increase in neointimal expansion observed in low-flow vs high-flow grafts is a subset of differentially expressed p27(kip1)-associated genes that correlate with critical stages in the adaptive response. These represent potential biologic targets whose activity may be altered to augment maladaptive vascular remodeling.

Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells

Local (cell-level) signaling environments, regulated by autocrine and paracrine signaling, and modulated by cell organization, are hypothesized to be fundamental stem cell fate control mechanisms used during development. It has, however, been challenging to demonstrate the impact of cell-level organization on stem cell fate control and to relate stem cell fate outcomes to autocrine and paracrine signaling. We address this fundamental problem using a combined in silico and experimental approach in which we directly manipulate, using laminar fluid flow, the local impact of endogenously secreted gp130-activating ligands and their activation of signal transducer and activator of transcription3 (STAT3) signaling in mouse embryonic stem cells (mESC). Our model analysis predicted that flow-dependent changes in autocrine and paracrine ligand binding would impact heterogeneity in cell- and colony-level STAT3 signaling activation and cause a gradient of cell fate determination along the direction of flow. Interestingly, analysis also predicted that local cell density would be inversely proportional to the degree to which endogenous secretion contributed to cell fate determination. Experimental validation using functional activation of STAT3 by secreted factors under microfluidic perfusion culture demonstrated that STAT3 activation and consequently mESC fate were manipulable by flow rate, position in the flow field, and local cell organization. As a unique demonstration of how quantitative control of autocrine and paracrine signaling can be integrated with spatial organization to elicit higher order cell fate effects, this work provides a general template to investigate organizing principles due to secreted factors.

Partial Meniscectomy Changes Fluid Pressurization in Articular Cartilage in Human Knees

Partial meniscectomy is believed to change the biomechanics of the knee joint through alterations in the contact of articular cartilages and menisci. Although fluid pressure plays an important role in the load support mechanism of the knee, the fluid pressurization in the cartilages and menisci has been ignored in the finite element studies of the mechanics of meniscectomy. In the present study, a 3D fibril-reinforced poromechanical model of the knee joint was used to explore the fluid flow dependent changes in articular cartilage following partial medial and lateral meniscectomies. Six partial longitudinal meniscectomies were considered under relaxation, simple creep, and combined creep loading conditions. In comparison to the intact knee, partial meniscectomy not only caused a substantial increase in the maximum fluid pressure but also shifted the location of this pressure in the femoral cartilage. Furthermore, these changes were positively correlated to the size of meniscal resection. While in the intact joint, the location of the maximum fluid pressure was dependent on the loading conditions, in the meniscectomized joint the location was predominantly determined by the site of meniscal resection. The partial meniscectomy also reduced the rate of the pressure dissipation, resulting in even larger difference between creep and relaxation times as compared to the case of the intact knee. The knee joint became stiffer after meniscectomy because of higher fluid pressure at knee compression followed by slower pressure dissipation. The present study indicated the role of fluid pressurization in the altered mechanics of meniscectomized knees.

Comparison of cardiac output determined by bioimpedance and bioreactance methods at rest and during exercise

Bioreactance is a novel non-invasive method for cardiac output measurement that involves the analysis of blood flow-dependent changes in the phase shifts of electrical currents applied across the chest. The present study (1) compared resting and exercise cardiac outputs determined by bioreactance and bioimpedance methods and those estimated from measured oxygen consumption, (2) determined the relationship between cardiac output and oxygen consumption, and (3) assessed the agreement between the bioreactance and bioimpedance methods. Twelve healthy subjects (aged 30±4years) performed graded cardiopulmonary exercise test on a recumbent cycle ergometer on two occasions, 1week apart. Cardiac output was monitored at rest, at 30, 50, 70, 90, 150W and at peak exercise intensity by bioreactance and bioimpedance and expired gases collected. Resting cardiac output was not significantly different between the bioreactance and bioimpedance methods (6.2±1.4 vs. 6.5±1.4lmin(-1), P=0.42). During exercise cardiac outputs were correlated with oxygen uptake for both bioreactance (r=0.84, P<0.01) and bioimpedance techniques (r=0.82, P<0.01). At peak exercise bioimpedance estimated significantly lower cardiac outputs than both bioreactance and theoretically calculated cardiac output (14.3±2.6 vs. 17.5±5.2 vs. 16.9±4.9lmin(-1), P<0.05). Bland-Altman analyses including data from rest and exercise demonstrated that the bioimpedance method reported ~1.5lmin(-1) lower cardiac output than bioreactance with lower and upper limits of agreement of -2.98 to 5.98lmin(-1). Bioimpedance and bioreactance methods provide different cardiac output estimates, particularly at high exercise intensity, and therefore the two methods cannot be used interchangeably. In contrast with bioimpedance, bioreactance cardiac outputs are similar to those estimated from measured oxygen consumption.

Disturbed Cerebral Circulation during Opening of the Venoarterial Bypass Bridge in Extracorporeal Membrane Oxygenation

To describe the effects on cerebral blood flow velocity (CBFV) of intermittent opening of the venoarterial bridge (VA bridge) during venoarterial extracorporeal membrane oxygenation (VA-ECMO). Prospective study in 22 newborns during VA ECMO. CBFV was measured in the pericallosal artery by Doppler ultrasound. Changes in peak systolic flow velocity (PSV), end diastolic flow velocity (EDV) and time-averaged mean flow velocity (TAM) on day 1, 2, 3, and 5 and at low ECMO flow (50- 150 ml/min) were analyzed (mean percentage+/-standard deviation (t-tests, p<0.05)). Changes >25% were considered relevant. The relationship between changes in CBFV and ECMO flow rate (Pearson correlation, p<0.01) was studied. Opening of the VA bridge resulted in statistically significant and relevant decreases in PSV (35 +/- 18%), EDV (93 +/- 15%) and TAM (68 +/- 13%), persisting during the consecutive days of treatment. Smaller changes in CBFV at low ECMO flow were statistically significant and mostly relevant: PSV (15 +/- 7%), EDV (76 +/- 21%) and TAM (40 +/- 12%). Changes in CBFV were positively correlated to the ECMO flow. Use of the VA bridge results in significant and relevant ECMO flow-dependent changes in CBFV, persisting during the treatment. The VA bridge should be used in such a way as to allow regular unclamping to be omitted.

Ultrasound scattering from silica fume clusters: in-line shear flow dynamics ofhydrophilic or partially hydrophobic silica fume fillers in melts of non-polar polymericsystems

Shear flow dynamics of fractal aggregates are investigated by ultrasound scattering tostudy shear induced disruption processes of hydrophilic polydisperse silica fume fillers inmelts of non-polar polymeric systems (polypropylene). A rheo-acoustical modelin the low frequency scattering regime only involving structural parameters isproposed. Flow-dependent changes of the ultrasound scattering power per unit ofvolume from hydrophilic silica fume aggregates during extrusion are analyzed inthe frame of the proposed rheo-acoustical model. In a second part, equilibriumstructures of polymer coated silica fume fillers are investigated to elucidate thecoupled intra- and inter-filler interactions. Surface chemistry of silica fume fillerswas modified by grafting amphiphilic molecules with the same hydrophobic tail(long alkyl chains) and various hydrophilic polar heads (amine, carboxylic acid orhydroxyl groups) to obtain a range of hydrophobic fumed silica units. The effectsof the surface layer of tethered chains and the extent of the coating level in anon-polar liquid dispersion are analyzed within the framework of the mismatch inchemical nature or solubility parameters between grafted chains and continuouspolymer phase. Lastly, the ability of the ultrasound scattering technique to give aquantitative estimate of the critical disaggregation shear stress mainly representative ofthe particle surface adhesive energy in relation to filler surface modification isshown.

Unraveling the relationship between macula densa cell volume and luminal solute concentration/osmolality

At the macula densa, flow-dependent changes in luminal composition lead to tubuloglomerular feedback and renin release. Apical entry of sodium chloride in both macula densa and cortical thick ascending limb (cTAL) cells occurs via furosemide-sensitive sodium-chloride-potassium cotransport. In macula densa, apical entry of sodium chloride leads to changes in cell volume, although there are conflicting data regarding the directional change in macula densa cell volume with increases in luminal sodium chloride concentration. To further assess volume changes in macula densa cells, cTAL-glomerular preparations were isolated and perfused from rabbits, and macula densa cells were loaded with fluorescent dyes calcein and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate. Cell volume was determined with wide-field and multiphoton fluorescence microscopy. Increases in luminal sodium chloride concentration from 0 to 80 mmol/l at constant osmolality led to cell swelling in macula densa and cTAL cells, an effect that was blocked by luminal application of furosemide. However, increases in luminal sodium chloride concentration from 0 to 80 mmol/l with concomitant increases in osmolality caused sustained decreases in macula densa cell volume but transient increases in cTAL cell volume. Increases in luminal osmolality with urea also resulted in macula densa cell shrinkage. These studies suggest that, under physiologically relevant conditions of concurrent increases in luminal sodium chloride concentration and osmolality, there is macula densa cell shrinkage, which may play a role in the macula densa cell signaling process.

Lack of synergism between flow and ATP in stimulating increases in vascular endothelial cell [Ca2+

Stimulation of purinergic receptors and the evoked rise in endothelial cell calcium, initiate the release of various factors that can lead to vasodilation. Increasing the intraluminal rate of flow can also initiate endothelium-dependent vasorelaxation. In rat small mesenteric arteries, neither flow nor ATP alone can stimulate robust dilatation, yet when flow is introduced in the presence of luminal ATP, marked blood vessel relaxation can be obtained (Liu et al. Am. J. Physiol Heart Circ. Physiol. 2004; 286: –1695). Both P2X and P2Y receptors can mediate the action of ATP and these receptors are expressed on both endothelial and smooth muscle cells. Therefore to assess the direct contribution by the endothelium, endothelial cells were freshly isolated from rat small mesenteric arteries, and changes in intracellular levels in response to flow and purinerigic agonists measured using confocal microscopy. Consistent with the results obtained for vasodilatation in intact vessels, no flow-dependent changes in intracellular endothelial cell Ca2+ could be observed. ATP, ADPβ-S, Bz-ATP each stimulated robust and sustained increases in cytoplasmic Ca2+, but this was not dependent on flow. These data indicate that isolation of endothelial cells appears to bypass the requirement for the interaction between flow and purinergic receptor stimulation. This may be due to the importance of cell-cell interactions in the wall of the artery and/or a specific cytoskeletal arrangement. Supported by the Wellcome Trust, UK

Flow-Dependent Changes in Doppler-Derived Aortic Valve Effective Orifice Area Are Real and Not Due to Artifact

We sought to determine whether the flow-dependent changes in Doppler-derived valve effective orifice area (EOA) are real or due to artifact. It has frequently been reported that the EOA may vary with transvalvular flow in patients with aortic stenosis. However, the explanation of the flow dependence of EOA remains controversial and some studies have suggested that the EOA estimated by Doppler-echocardiography (EOA(Dop)) may underestimate the actual EOA at low flow rates. One bioprosthetic valve and three rigid orifices were tested in a mock flow circulation model over a wide range of flow rates. The EOA(Dop) was compared with reference values obtained using particle image velocimetry (EOA(PIV)). There was excellent agreement between EOA(Dop) and EOA(PIV) (r2 = 0.94). For rigid orifices of 0.5 and 1.0 cm2, no significant change in the EOA was observed with increasing flow rate. However, substantial increases of both EOA(Dop) and EOA(PIV) were observed when stroke volume increased from 20 to 70 ml both in the 1.5 cm2 rigid orifice (+52% for EOA(Dop) and +54% for EOA(PIV)) and the bioprosthetic valve (+62% for EOA(Dop) and +63% for EOA(PIV)); such changes are explained either by the presence of unsteady effects at low flow rates and/or by an increase in valve leaflet opening. The flow-dependent changes in EOA(Dop) are not artifacts but represent real changes in EOA attributable either to unsteady effects at low flow rates and/or to changes in valve leaflet opening. Such changes in EOA(Dop) can be relied on for clinical judgment making.

Rheology and Ultrasound Scattering from Aggregated Red Cell Suspensions in Shear Flow

The shear flow dynamics of reversible red cell aggregates in dense suspensions were investigated by ultrasound scattering, to study the shear disruption processes of Rayleigh clusters and examine the effective mean field approximation used in microrheological models. In a first section, a rheo-acoustical model, in the Rayleigh scattering regime, is proposed to describe the shear stress dependence of the low frequency scattered power in relation to structural parameters. The fractal scattering regime characterizing the anisotropic scattering from flocs of size larger than the ultrasound wavelength is further discussed. In the second section, we report flow-dependent changes in the low-frequency scattering coefficient in a plane-plane flow geometry to analyze the shear disruption processes of hardened or deformable red cell aggregates in neutral dextran polymer solution. Rheo-acoustical experiments are examined on the basis of the rheo-acoustical model and the effective medium approximation. The ability of ultrasound scattering technique to determine the critical disaggregation shear stress and to give quantitative information on particle surface adhesive energy is analyzed. Lastly, the shear-thinning behavior of weakly aggregated hardened or deformable red cells is described.

Blood flow-dependent changes in intrarenal nitric oxide levels during anesthesia with halothane or sevoflurane

We previously demonstrated that intrarenal nitric oxide (NO) levels and renal blood flow are reduced during halothane anesthesia. Studies were performed to determine if volatile anesthetics-induced reductions in renal NO levels are associated with blood flow changes. Halothane and sevoflurane at 0.8 and 2.4 Mac were administered by inhalation to dogs, and cGMP and NOx concentrations in the renal interstitial fluid were measured by a microdialysis method. Neither halothane nor sevoflurane at 0.8 Mac altered renal blood flow and renal interstitial cyclic guanosine monophosphate (cGMP) and NOx levels, but both anesthetics significantly decreased these values at 2.4 Mac. Using an adjustable aortic clamp, renal perfusion pressure was reduced in 2 steps without halothane and sevoflurane anesthesia. Renal blood flow as well as cGMP and NOx concentrations in the renal interstitial fluid were unchanged within the autoregulatory range, but significantly decreased below the autoregulatory range. Changes in cGMP and NOx concentrations in the renal interstitial fluid were highly correlated with renal blood flow changes during halothane or sevoflurane anesthesia, and during stepwise reductions in renal perfusion pressure. The results suggested that halothane- and sevoflurane-induced decreases in intrarenal NO levels result from reductions in blood flow.

Diffusion ultrasonore par des suspensions concentrées d'agrégats fractals de globules rouges dans un écoulement de cisaillement

Shear flow dynamics of reversible fractal clusters in dense suspensions were investigated by ultrasound scattering to study shear disruption processes of Rayleigh aggregates and further examine the effective mean field approximation used in the microrheological models. Within the framework of a fractal flocculation process, the concept of variance in local particle volume fraction is used to derive an original expression of the ultrasonic backscattering cross-section for a dense distribution of correlated Rayleigh fractal clusters. Considering the scaling laws for shear break-up of reversible aggregates in concentrated suspensions, a rheo-acoustical model in the Rayleigh scattering regime is proposed to describe the shear stress dependence of the low frequency backscattering coefficient with physical parameters. The anisotropic scattering effects from flocs of size larger than ultrasound wavelength are further discussed. In a second part, we report flow dependent changes of the ultrasonic backscattering coefficient in a plane–plane flow geometry to analyze shear break-up processes of hardened or deformable red cell aggregates in dextran solutions. Rheo-acoustical experiments were examined on the basis of the rheo-acoustial model and the effective medium approximation. The ability of ultrasound scattering to determine the critical shear stress and to give quantitative information on particle surface adhesive energy is analyzed.

Sequential assessment of mitral valve area during diastole using colour M-mode flow convergence analysis: new insights into mitral stenosis physiology.

In mitral stenosis (MS) transvalvular flow and velocity continually change throughout diastole but for mitral valve area (MVA), flow-dependent variations (valve reserve) are unknown. These physiologic changes can be studied by the proximal isovelocity surface area (PISA) method, using the high temporal resolution of colour M-mode, essential for simultaneous measurements of flow and velocity. Hence, we aimed to validate the colour M-mode PISA method for measurement of MVA in MS and to define using this method the physiologic flow-dependent changes of MVA during diastole. In 50 patients with native MS, MVA was measured by planimetry (MVA-2D), Doppler pressure half-time (MVA-PHT), and two-dimensional PISA (2D-PISA). MVA measurement by colour M-mode PISA in early diastole (M-PISA) (1.27+/-0.46 cm(2)) with rigorously timed flow and velocity measurements by continuous wave Doppler did not differ and correlated well with MVA-2D (1.29+/-0.44 cm(2), p=0.59; r=0.85, p<0.001) and MVA-PHT (1.30+/-0.41 cm(2), p=0.52; r=0.80, p<0.001). In contrast a trend towards underestimation of MVA by 2D-PISA was observed (1.23+/-0.42 cm(2); p=0.10 and p=0.07). Timed analysis of transvalvular haemodynamics at early, mid, mid-late, and late diastole showed marked changes in flow and velocities (both p<0.0001) but not in MVA (respectively 1.27+/-0.46, 1.29+/-0.47, 1.28+/-0.51 and 1.27+/-0.49 cm(2); ns). In MS, the high temporal resolution of colour M-mode PISA allows accurate MVA measurements. It also allows for the first time, sequential MVA assessment during diastole. Notwithstanding marked flow and velocities changes, MVA remained unchanged throughout diastole underscoring the lack of flow-related valvular reserve in MS.

Flow-induced neointimal regression in baboon polytetrafluoroethylene grafts is associated with decreased cell proliferation and increased apoptosis.

We have previously shown that baboon grafts subjected to elevated shear stress exhibit an increase in luminal area through atrophy of the neointimal layer. This study was designed to investigate the smooth muscle cell (SMC) growth kinetics during early regression and evaluate the influence of nitric oxide (NO) in the regulation of this process. Sixteen baboons underwent bilateral polytetrafluorethylene aortoiliac graft placement. After development of a neointima over an 8-week period, blood flow through one graft was increased with placement of a downstream arteriovenous fistula. Grafts were harvested at 4 (n = 6), 7 (n = 5), and 14 (n = 5) days and assessed for neointimal cross-sectional area, SMC proliferation and apoptosis, and macrophage infiltration. High-flow grafts were compared with contralateral normal-flow controls. Eleven baboons underwent an identical experimental preparation to evaluate the effect of NO inhibition. Eight weeks after graft implantation, the animals were treated with an initial bolus (100 mg/kg) followed by continuous infusion (60 mg/kg/d) of either N(G)-nitro-L-arginine methyl ester (L-NAME; n = 6) or the inactive stereoisomer N(G)-nitro-D-arginine methyl ester (n = 5). Grafts were harvested at 7 days and evaluated with the experimental endpoints detailed previously. Distal fistula placement resulted in a 3.8-fold increase in mean centerline velocity and wall shear stress. Grafts harvested during the initial 14 days after flow manipulation showed a progressive reduction in neointimal cross-sectional area. This change was associated with a decrease in subendothelial SMC proliferation and an increase in neointimal SMC apoptosis, the latter being in the region adjacent to the graft. Animals treated with L-NAME showed a 20% reduction in platelet cyclic guanosine monophosphate and a 17% reduction in serum nitrate/nitrite concentrations. Despite this inhibition of NO production, no effect on the flow-dependent changes in neointimal area, cell proliferation, or apoptosis was observed in the L-NAME-treated baboons. The local hemodynamic environment within healing prosthetic grafts modulates neointimal SMC proliferation and apoptosis. An increase in graft flow leads to atrophy of the neointima.

Quantifying Flow-Dependent Changes in Subyearling Fall Chinook Salmon Rearing Habitat Using Two-Dimensional Spatially Explicit Modeling

Abstract We used an analysis based on a geographic information system (GIS) to determine the amount of rearing habitat and stranding area for subyearling fall chinook salmon Oncorhynchus tshawytscha in the Hanford Reach of the Columbia River at steady-state flows ranging from 1,416 to 11,328 m3/s. High-resolution river channel bathymetry was used in conjunction with a two-dimensional hydrodynamic model to estimate water velocities, depths, and lateral slopes throughout our 33-km study area. To relate the probability of fish presence in nearshore habitats to measures of physical habitat, we developed a logistic regression model from point electrofishing data. We only considered variables that were compatible with a GIS and therefore excluded other variables known to be important to juvenile salmonids. Water velocity and lateral slope were the only two variables included in our final model. The amount of available rearing habitat generally decreased as flow increased, with the greatest decreases occurring b...

Effects of haemoconcentration and haemodilution on acute hypoxia-induced pulmonary hypertension and changes in vascular compliance of isolated rabbit lungs.

Erythrocytes influence the magnitude of hypoxia-induced pulmonary artery pressure increase. It is, however, unknown to what extent haemoconcentration and haemodilution affect this response and whether intrapulmonary blood volume (and thus vessel dimensions) alters the magnitude of pressure increase. Furthermore, it is unclear whether the haemodilution/ haemoconcentration-dependent pressure increase is flow-related, via flow-dependent changes in vasomotor tone or rheologic effects, or can also be observed under no-flow conditions. Experimental study in isolated rabbit lungs (n = 12) perfused with autologous blood at constant flow (100 ml/min) and ventilated with 5% carbon dioxide in air. Laboratory for experimental studies. Haemoconcentration (centrifugation) and haemodilution (Krebs-Henseleit/albumin) were carried out, resulting in haematocrits between 50% and 0%. During hypoxic ventilation, inspiratory oxygen fraction was reduced from 0.20 to 0.03. Under constant flow conditions, haemodilution (from a Hct of 34-36% to 0-1%) decreased hypoxic pulmonary artery pressure response to one-third (from 10.8 +/- 2.3 cmH2O to 3.1 +/- 1.0 cmH2O, P < 0.05), while haemoconcentration did not affect the magnitude of hypoxic response (10.5 +/- 2.0 cmH2O). For all haematocrit values an increase in pulmonary blood volume (by 5 ml) decreased the magnitude of pressure response. Hypoxia-induced changes in static vascular filling pressure (double occlusion pressure) and vascular compliance were used to assess the strength of hypoxic vasoconstriction under static conditions. Neither haemoconcentration nor haemodilution altered hypoxia-induced changes in either variable. The magnitude of the acute hypoxic pressure response is not altered by haemoconcentration, but significantly reduced by haemodilution. In contrast, neither haemoconcentration nor haemodilution influenced hypoxia-induced changes in static vascular filling pressure and compliance. This suggests that the degree of hypoxic pulmonary vasoconstriction is not affected under static conditions and that the red blood cell-dependence of the magnitude of hypoxic pressure response is based on flow-related mechanisms.