Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordVascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (−44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.National Institute of HealthNational Institute for Health Research (NIHR

Sustainable flood risk and stormwater management in blue‐green cities; an interdisciplinary case study in Portland, Oregon

Blue-Green Infrastructure (BGI) is recognized as a viable strategy to manage stormwater and flood risk, and its multifunctionality may further enrich society through the provision of multiple cobenefits that extend far beyond the hydrosphere. Portland, Oregon, is an internationally renowned leader in the implementation of BGI and showcases many best practice examples. Nonetheless, a range of interdisciplinary barriers and uncertainties continue to cloud decision making and impede wider implementation of BGI. In this paper, we synthesize research conducted by the “Clean Water for All” (CWfA) research project and demonstrate that interdisciplinary evaluation of the benefits of Portland’s BGI, focusing on green street bioswales and the East Lents Floodplain Restoration Project, is essential to address biophysical and sociopolitical barriers. Effective interdisciplinary approaches require sustained interaction and collaboration to integrate disciplinary expertise toward a common problem-solving purpose, and strong leadership from researchers adapt at spanning disciplinary boundaries. While the disciplinary differences in methodologies were embraced in the CWfA project, and pivotal to providing evidence of the disparate benefits of multifunctional BGI, cross-disciplinary engagement, knowledge coproduction, and data exchanges during the research process were of paramount importance to reduce the potential for fragmentation and ensure research remained integrated. © 2020 The Authors. Journal of the American Water Resources Association published by Wiley Periodicals LLC on behalf of American Water Resources Associatio

SBC2007-175993 MEASUREMENT OF IN-VIVO PULMONARY VASCULAR IMPEDANCE IN TWO ANIMAL MODELS OF PULMONARY HYPERTENSION

INTRODUCTION Pulmonary vascular input impedance has been increasingly promoted as an important diagnostic for pulmonary arterial hypertension (PAH) The human studies noted above have understandably not examined detailed associations between impedance and vascular behavior and structure, since the latter data are obtainable only through focused drug studies or ex-vivo measurements. Mechanical changes to a vascular network should be reflected in its input impedance; thus, such investigation should be useful in determining how impedance varies with changes in vascular condition, such as chronic stiffening due to vascular remodeling or acute stiffening due to smooth muscle cell response and/or pressure-induced strain-stiffening. Naturally, clinical identification of such stiffness changes on a routine basis could greatly impact diagnosis. Here, we demonstrate simple-toimplement impedance measurements in two animal models as part of a larger effort to establish said links between clinically-viable diagnostics, such as impedance, and physiological changes that occur to the vasculature as part of the progression of PAH. METHODS Animal Preparation: The two animal models examined here develop PAH due to chronic exposure to a hypoxic environment. The first model consisted of 10 male Sprague-Dawley rats (300-400g), half exposed to hypoxia via hypobaric chamber for 3-4 weeks (barometric pressure ≈ 410 mmHg) and half retained at standard conditions in Denver, CO (barometric pressure ≈ 630 mmHg). The second model utilized 4 male Holstein calves (70-110lb), again with half exposed to hypoxia for two weeks (barometric pressure ≈ 460 mmHg) and the other half remaining normoxic. Both models were exposed to a 12:12-h light-dark cycle, and water and appropriate food were made available ad libitum. Animal care and use committees at both the University of Colorado Health Science Center (rat) and Colorado State University (calf) approved all protocols and procedures. Animal Data Collection and Analysis: The measurements obtained from each animal are identical; the main differences between collection methods are equipment size and type. For all measurements, rats are anesthetized with ketamine hydrochloride (40 mg/kg) and xylazine (10 mg/kg) intraperitoneally, while cows remain conscious. Right jugular access is then obtained in each animal, and a fluid filled catheter, consisting of PV1 tubing for the rat or a commercial Swan-Ganz catheter for the calf, is inserted into the main pulmonary artery (MPA) for pressure measurements. During collection of MPA pressure, blood velocity at the midline of the MPA is obtained with pulse-wave Doppler echocardiography using an FPA probe on a commercial ultrasound scanner (Vivid 5, GE Medical Systems Inc). The imaging depth dictates the probe frequency

Impact of pericardial adhesions on diastolic function as assessed by vortex formation time, a parameter of transmitral flow efficiency

<p>Abstract</p> <p>Background</p> <p>Pericardial adhesions are a pathophysiological marker of constrictive pericarditis (CP), which impairs cardiac filling by limiting the total cardiac volume compliance and diastolic filling function. We studied diastolic transmitral flow efficiency as a new parameter of filling function in a pericardial adhesion animal model. We hypothesized that vortex formation time (VFT), an index of optimal efficient diastolic transmitral flow, is altered by patchy pericardial-epicardial adhesions.</p> <p>Methods</p> <p>In 8 open-chest pigs, the heart was exposed while preserving the pericardium. We experimentally simulated early pericardial constriction and patchy adhesions by instilling instant glue into the pericardial space and using pericardial-epicardial stitches. We studied left ventricular (LV) function and characterized intraventricular blood flow with conventional and Doppler echocardiography at baseline and following the experimental intervention.</p> <p>Results</p> <p>Significant decreases in end-diastolic volume, ejection fraction, stroke volume, and late diastolic filling velocity reflected the effects of the pericardial adhesions. The mean VFT value decreased from 3.61 ± 0.47 to 2.26 ± 0.45 (P = 0.0002). Hemodynamic variables indicated the inhibiting effect of pericardial adhesion on both contraction (decrease in systolic blood pressure and +dP/dt decreased) and relaxation (decrease in the magnitude of -dP/dt and prolongation of Tau) function.</p> <p>Conclusion</p> <p>Patchy pericardial adhesions not only negatively impact LV mechanical functioning but the decrease of VFT from normal to suboptimal value suggests impairment of transmitral flow efficiency.</p

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC) and adult-derived (aNPC) neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation