Numerical simulation of steady turbulent flow through trileaflet aortic heart valves—I. Computational scheme and methodology

A numerical simulation model and technique are described to simulate steady turbulent blood flow through trileaflet tissue valves of varying degrees of stenosis. The aortic trileaflet tissue valve design was chosen as the subject of this study, since it is the only popular valve in current clinical use which is approximately axisymmetric. An axisymmetric geometry is computationally more convenient since it involves only two dimensional equations. The geometry and dimensions of the aorta were designed from angiographic studies and measurements made from cadavers. The valve dimensions were obtained from tissue leaflet photography studies conducted on tissue bioprostheses of varying degrees of stenosis. The nonrectangular nature of this valve necessitated the use of a body conforming grid. Thompson's method coupled with a Chimera grid system was chosen for this purpose. The Chimera grid was used to avoid a grid with highly skewed cells. Turbulence was simulated by using the k- model with the wall function method. This decision was made after comparing the k- model's performance with that of lower order models, and after considering the increased computer time requirements and decreased stability of more complex models, such as the Reynolds stress model. The results of the study which are very encouraging and compare favorably with in vitro experimental data, are described in Part II of the paper.     

Turbulent shear stress measurements in the vicinity of aortic heart valve prostheses

A two dimensional laser Doppler anemometer system has been used to measure the turbulent shear fields in the immediate downstream vicinity of a variety of mechanical and bioprosthetic aortic heart valves. The measurements revealed that all the mechanical valves studied, created regions of elevated levels of turbulent shear stress during the major portion of systole. The tissue bioprostheses also created elevated levels of turbulence, but they were confined to narrow regions in the bulk of the flow field. The newer generation of bioprostheses create turbulent shear stresses which are considerably lower than those created by the older generation tissue valve designs. All the aortic valves studied (mechanical and tissue) create turbulent shear stress levels which are capable of causing sub-lethal and/or lethal damage to blood elements.     

Three-dimensional computational model of left heart diastolic function with fluid-structure interaction

Aided by advancements in computer speed and modeling techniques, computational modeling of cardiac function has continued to develop over the past twenty years. The goal of the current study was to develop a computational model that provides blood-tissue interaction under physiologic flow conditions, and apply it to a thin-walled model of the left heart. To accomplish this goal, the Immersed Boundary Method was used to study the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology. The fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). A left heart model was developed to examine diastolic function, and consisted of the left ventricle, left atrium, and pulmonary flow. The input functions for the model included the pulmonary driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions for validation. The inflow velocities through the mitral valve corresponded with clinical values (E-wave = 74.4 cm/s, A-wave = 43 cm/s, and E/A = 1.73). The pressure traces for the atrium and ventricle, and the appearance of the ventricular flow fields throughout filling, agreed with those observed in the heart. In addition, the atrial flow fields could be observed in this model and showed the conduit and pump functions that current theory suggests. The ability to examine atrial function in the present model is something not described previously in computational simulations of cardiac function.     

Separation and Characterization of the Activated Pool of Colony-Stimulating Factor 1 Receptor Forming Distinct Multimeric Complexes with Signalling Molecules in Macrophages

Colony-stimulating factor 1 (CSF-1) triggers the activation of intracellular proteins in macrophages through selective assembly of signalling complexes. The separation of multimeric complexes of the CSF-1 receptor (CSF-1R) by anion-exchange chromatography enabled the enrichment of low-stoichiometry complexes. A significant proportion of the receptor in CSF-1-stimulated cells that neither possessed detectable tyrosine kinase activity nor formed complexes was separated from the receptor pool displaying autokinase activity that formed chromatographically distinct multimeric complexes. A small pool of CSF-1R formed a multimeric complex with phosphatidylinositol-3 kinase (PI-3 kinase), SHP-1, Grb2, Shc, c-Src, Cbl, and a significant number of tyrosine-phosphorylated proteins in CSF-1-stimulated cells. The complex showed a considerable amount of CSF-1R complex-associated kinase activity. A detectable level of the complex was also present in untreated cells. PI-3 kinase in the multimeric complex displayed low lipid kinase activity despite the association with several proteins. The major pool of activated CSF-1R formed transient multimeric complexes with distinctly different tyrosine-phosphorylated proteins, which included STAT3 but also PI-3 kinase, Shc, SHP-1, and Grb2. A significant level of lipid kinase activity was detected in PI-3 kinase in the latter complexes. The different specific enzyme activities of PI-3 kinase in these complexes support the notion that the activity of PI-3 kinase is modulated by its association with CSF-1R and other associated cellular proteins. Specific structural proteins associated with the separate CSF-1R multimeric complexes upon CSF-1 stimulation and the presence of the distinct pools of the CSF-1R were dependent on the integrity of the microtubular network.     

Cellular localization and age dependent changes in mRNA for glutathione S-transferase-P in rat testicular cells

Using Northern blotting techniques we report that mRNA for Glutathione S-transferase-P (GST-P or GST 7-7) is present in rat testis. GST-P mRNA was detected in cultured Sertoli cells, cultured peritubular cells, as well as in transplantable Leydig cell tumor. However, no GST-P mRNA was detected in rat germ cell fractions. There was a marked increase in mRNA for GST-P from day 5 to day 20 in rats, after which a decrease was seen. The decreased level of mRNA for GST-P in the testis after 20 days of age, coincided in time with the exponential increase in germ cells, and accompanying relative decrease in somatic cells. The results show that mRNA for GST-P is primarily present in somatic cells of the rat testis.     

Experimental technique of measuring dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm2) but elevated to its peak during mid to late systole at about 18-20 dyn/cm2. Low magnitude shear stress (<5 dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.     

The effectiveness of evidence summaries on health policymakers and health system managers use of evidence from systematic reviews: a systematic review

Background

Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which make them hard to use for decision-making. There are many organizations that develop and disseminate derivative products, such as evidence summaries, from systematic reviews for different populations or subsets of decision makers. This systematic review aimed to (1) assess the effectiveness of evidence summaries on policymakers’ use of the evidence and (2) identify the most effective summary components for increasing policymakers’ use of the evidence. We present an overview of the available evidence on systematic review derivative products.

Methods

We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of “evidence summary,” “policy brief,” or other products derived from systematic reviews that presented evidence in a summarized form. The primary outcomes were the (1) use of systematic review summaries in decision-making (e.g., self-reported use of the evidence in policymaking and decision-making) and (2) policymakers’ understanding, knowledge, and/or beliefs (e.g., changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g., format) of the summaries.

Results

Our database search combined with our gray literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text, and we included six studies (reported in seven papers) as well as protocols from two ongoing studies. Two studies assessed the use of evidence summaries in decision-making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (four studies), and perceived usefulness or usability (three studies). Summary of findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for summary of findings tables, certain elements, such as reporting study event rates and absolute differences, were preferred as well as avoiding the use of footnotes.

Conclusions

Evidence summaries are likely easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear.

Trial registration

The protocol was published in the journal Systematic Reviews (2015;4:122)