Flow recirculation zone length and shear rate are differentially affected by stenosis severity in human coronary arteries.

Flow recirculation zones and shear rate are associated with distinct pathogenic biological pathways relevant to thrombosis and atherogenesis. The interaction between stenosis severity and lesion eccentricity in determining the length of flow recirculation zones and peak shear rate in human coronary arteries in vivo is unclear. Computational fluid dynamic simulations were performed under resting and hyperemic conditions on computer-generated models and three-dimensional (3-D) reconstructions of coronary arteriograms of 25 patients. Boundary conditions for 3-D reconstructions simulations were obtained by direct measurements using a pressure-temperature sensor guidewire. In the computer-generated models, stenosis severity and lesion eccentricity were strongly associated with recirculation zone length and maximum shear rate. In the 3-D reconstructions, eccentricity increased recirculation zone length and shear rate when lesions of the same stenosis severity were compared. However, across the whole population of coronary lesions, eccentricity did not correlate with recirculation zone length or shear rate (P = not signficant for both), whereas stenosis severity correlated strongly with both parameters (r = 0.97, P < 0.001, and r = 0.96, P < 0.001, respectively). Nonlinear regression analyses demonstrated that the relationship between stenosis severity and peak shear was exponential, whereas the relationship between stenosis severity and recirculation zone length was sigmoidal, with an apparent threshold effect, demonstrating a steep increase in recirculation zone length between 40% and 60% diameter stenosis. Increasing stenosis severity and lesion eccentricity can both increase flow recirculation and shear rate in human coronary arteries. Flow recirculation is much more sensitive to mild changes in the severity of intermediate stenoses than is peak shear.

Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel.

Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activation within human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel. A novel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined. We provide evidence of intracoronary up-regulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.

Comparative life cycle assessment of system solution scenarios for residual municipal solid waste management in NSW, Australia.

Life cycle assessment (LCA) is a promising tool to evaluate the environmental impacts of different technologies for sustainable waste management. This study employs LCA to assess environmental impacts of alternative scenarios for residual municipal solid waste (MSW) management in New South Wales (NSW) based on current conditions and policies. Six different scenarios including a baseline scenario (landfilling) were applied for NSW waste management for energy production and their impacts on environment. The initial results showed that the scenario 3 that employed anaerobic digestion for food waste, incineration for combustible waste and plastic waste, and landfilling for non-combustible waste produced electricity of 625 kWh/t, which was maximum compared to the other scenarios. LCA results further suggested that among all scenarios, scenario 5 (similar to scenario 3 except combustible waste was treated through gasification and plastic waste was recycled) has the lowest level of environmental burdens in global warming, freshwater and marine ecotoxicity, and human non-carcinogenic toxicity. The sensitivity analysis for energy conversion rates (23-30%) for incineration and plastic recycling rate (66-91.3%) for MSW was further conducted and the results showed that energy conversion rate of 30% makes scenario 3 more valuable for electricity generation and less impactful for ecosystems damage category compared to scenario 5. On the other hand, plastic recycling rate of 91.3% has the lowest environmental burdens and by decreasing recycling rate to 66% the environmental impacts increase; however, it was noticed that reduction in recycling rate does not make any change in the order of scenarios. Overall, the study suggests that each waste type in NSW should be treated with a specific technology to achieve the highest resource recovery and lowest environmental impacts where energy conversion and plastic recycling rates have significant impacts.

Using postgraduate students' evaluations of research experience to benchmark departments and faculties: issues and challenges.

BACKGROUND: The introduction of the Australian Research Training Scheme has been a strong reason for assuring the quality of the research higher degree (RHD) experience; if students experience poor supervision, an unsupportive climate, and inadequate infrastructure, prior research suggests RHD students will be less likely to complete their degree, with negative consequences for the student, the university, and society at large. AIMS: The present study examines the psychometric properties of a survey instrument, the Student Research Experience Questionnaire (SREQ), for measuring the RHD experience of currently enrolled students. The core scales of the SREQ focus on student experiences of Supervision; Infrastructure; Intellectual and Social Climate; and Generic Skills Development. SAMPLE: Participants were 2,213 postgraduate research students of a large, research-intensive Australian university. RESULTS: Preliminary factor analyses conducted at the student level supported the a priori four factors that the SREQ was designed to measure. However, multi-level analyses indicated that there was almost no differentiation between faculties or departments nested with faculties, suggesting that the SREQ responses are not appropriate for benchmarking faculties or departments. CONCLUSIONS: Consistent with earlier research based on comparisons across universities, the SREQ is shown to be almost completely unreliable in terms of benchmarking faculties or departments within a university.

Effect of magnetic field on haemodynamic perturbations in atherosclerotic coronary arteries.

Haemodynamic perturbations including elevated blood viscosity, low and oscillatory shear stress are understood to be important pathogenic mediators in atherosclerosis. These haemodynamic abnormalities are influenced by the presence of a magnetic field. This study conducted computational fluid dynamics (CFD) analysis in 4 coronary artery models, derived from authentic human coronaries, with mild and moderate and severe stenosis severity. The aim was to investigate the effect of a static magnetic field of varying intensities on blood viscosity, areas of low wall shear stress (ALWSS), maximum wall shear stress (MWSS) and length and volume of flow recirculation zones. The results showed that the magnetic field results in both beneficial and detrimental changes in haemodynamics. The beneficial effects are lowered viscosity, decreased size of ALWSS and flow recirculation zones whereas the detrimental effect is increased MWSS. With increasing stenosis severity the effect of magnetic field becomes more prominent. An externally applied magnetic field can improve haemodynamics perturbations in human coronary arteries, especially in the setting of moderate-to-severe stenosis severity.

Generation of sclerosant foams by mechanical methods increases the foam temperature.

Objective To investigate the effect of agitation on foam temperature. Methods Sodium tetradecyl sulphate and polidocanol were used. Prior to foam generation, the sclerosant and all constituent equipment were cooled to 4-25℃ and compared with cooling the sclerosant only. Foam was generated using a modified Tessari method. During foam agitation, the temperature change was measured using a thermocouple for 120 s. Results Pre-cooling all the constituent equipment resulted in a cooler foam in comparison with only cooling the sclerosant. A starting temperature of 4℃ produced average foam temperatures of 12.5 and 13.2℃ for sodium tetradecyl sulphate and polidocanol, respectively. It was also found that only cooling the liquid sclerosant provided minimal cooling to the final foam temperature, with the temperature 20 and 20.5℃ for sodium tetradecyl sulphate and polidocanol, respectively. Conclusion The foam generation process has a noticeable impact on final foam temperature and needs to be taken into consideration when creating foam.

Haemodynamic assessment of human coronary arteries is affected by degree of freedom of artery movement.

Abnormal haemodynamic parameters are associated with atheroma plaque progression and instability in coronary arteries. Flow recirculation, shear stress and pressure gradient are understood to be important pathogenic mediators in coronary disease. The effect of freedom of coronary artery movement on these parameters is still unknown. Fluid-structure interaction (FSI) simulations were carried out in 25 coronary artery models derived from authentic human coronaries in order to investigate the effect of degree of freedom of movement of the coronary arteries on flow recirculation, wall shear stress (WSS) and wall pressure gradient (WPG). Each FSI model had distinctive supports placed upon it. The quantitative and qualitative differences in flow recirculation, maximum wall shear stress (MWSS), areas of low wall shear stress (ALWSS) and maximum wall pressure gradient (MWPG) for each model were determined. The results showed that greater freedom of movement was associated with lower MWSS, smaller ALWSS, smaller flow recirculation zones and lower MWPG. With increasing percentage diameter stenosis (%DS), the effect of degree of freedom on flow recirculation and WSS diminished. Freedom of movement is an important variable to be considered for computational modelling of human coronary arteries, especially in the setting of mild to moderate stenosis. ABBREVIATIONS: 3D: Three-dimensional; 3DR: Three-dimensional Reconstruction; 3D-QCA: Three-dimensional quantitative coronary angiography; ALWSS: Areas of low wall shear stress; CAD: Coronary artery disease; CFD: Computational fluid dynamics; %DS: Diameter stenosis percentage; EPCS: End point of counter-rotating streamlines; FSI: Fluid-structure interaction; IVUS: Intravascular ultrasound; LAD: Left anterior descending; MWSS: Maximum wall shear stress; SST: Shear stress transport; TAWSS: Time-averaged wall shear stress; WSS: wall shear stress; WPG: Wall pressure gradient; MWPG: Maximum wall pressure gradient; FFR: Fractional flow reserve; iFR: Instantaneous wave-free ratio.

A new approach to blood flow simulation in vascular networks.

A proper analysis of blood flow is contingent upon accurate modelling of the branching pattern and vascular geometry of the network of interest. It is challenging to reconstruct the entire vascular network of any organ experimentally, in particular the pulmonary vasculature, because of its very high number of vessels, complexity of the branching pattern and poor accessibility in vivo. The objective of our research is to develop an innovative approach for the reconstruction of the full pulmonary vascular tree from available morphometric data. Our method consists of the use of morphometric data on those parts of the pulmonary vascular tree that are too small to reconstruct by medical imaging methods. This method is a three-step technique that reconstructs the entire pulmonary arterial tree down to the capillary bed. Vessels greater than 2 mm are reconstructed from direct volume and surface analysis using contrast-enhanced computed tomography. Vessels smaller than 2 mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray's laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray's laws to every vessel bifurcation simultaneously leads to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the first capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-defined Strahler system, are assigned. In conclusion, the present model provides a morphological foundation for future analysis of blood flow in the pulmonary circulation.

Basic physiochemical and rheological properties of detergent sclerosants.

OBJECTIVES: To determine the basic physiochemical properties and rheological activity of detergent sclerosants. METHODS: Sodium tetradecyl sulphate and polidocanol liquid and foam sclerosants were investigated in a range of concentrations (0.1-3%), liquid-plus-air fractions (1+2 to 1+8) and dilutions in water (stock solutions) or in normal saline. The embolic agent ethanol was investigated for comparison. Density was measured using a digital balance. Surface tension was measured by the Du Nuoy ring method and used to determine the critical micellar concentration. Viscosity was measured using a cone-plate rheometer for liquid and a modified parallel plate method for foam. RESULTS: Liquid sclerosant density decreased as the sclerosant concentration increased while foam density decreased with the increasing air fraction. The critical micellar concentration of polidocanol was 0.002% in both normal saline and water while that of sodium tetradecyl sulphate was 0.075% in normal saline and 0.200% in water. Viscosity of liquid sodium tetradecyl sulphate was lower than that of polidocanol. Foam sclerosants were at least 10,000-fold more viscous than liquid sclerosants and ethanol. All agents demonstrated a Non-Newtonian shear-thinning behaviour with a fall in viscosity at lower shear rates (<10 s(-1)). Polidocanol (but not sodium tetradecyl sulphate) foam viscosity progressively increased with increasing sclerosant concentration and liquid-plus-air fractions. CONCLUSIONS: Liquid and foam sclerosants and ethanol are Non-Newtonian shear thinning fluids. Foam sclerosants are significantly more viscous than liquid agents.

Correlation between Reynolds number and eccentricity effect in stenosed artery models.

BACKGROUND: Flow recirculation and shear strain are physiological processes within coronary arteries which are associated with pathogenic biological pathways. Distinct Quite apart from coronary stenosis severity, lesion eccentricity can cause flow recirculation and affect shear strain levels within human coronary arteries. OBJECTIVE: The aim of this study is to analyse the effect of lesion eccentricity on the transient flow behaviour in a model of a coronary artery and also to investigate the correlation between Reynolds number (Re) and the eccentricity effect on flow behaviour. METHODS: A transient particle image velocimetry (PIV) experiment was implemented in two silicone based models with 70% diameter stenosis, one with eccentric stenosis and one with concentric stenosis. RESULTS: At different times throughout the flow cycle, the eccentric model was always associated with a greater recirculation zone length, maximum shear strain rate and maximum axial velocity; however, the highest and lowest impacts of eccentricity were on the recirculation zone length and maximum shear strain rate, respectively. Analysis of the results revealed a negative correlation between the Reynolds number (Re) and the eccentricity effect on maximum axial velocity, maximum shear strain rate and recirculation zone length. CONCLUSIONS: As Re number increases the eccentricity effect on the flow behavior becomes negligible.

Correlation of Stroke Volume Measurement between Sonosite Portable Echocardiogram and Edwards Flotrac Sensor-Vigileo Monitor in an Intensive Care Unit.

PURPOSE: Stroke volume (SV) is a parameter that is being recognized as an endpoint in fluid resuscitation algorithms. Its role is now being realized as an important variable in hemodynamic assessment in various clinical scenarios such as septic and cardiogenic shocks. Direct measurement of stroke volume (SV) and its novel corollary, stroke volume variation (SVV) derived by proprietary software, are preferred over mean cardiac output (CO) measurements because they render a more accurate reflection of hemodynamic status independent of heart rate. Flotrac-Vigileo monitor (FTV) (Edwards Lifesciences, Irvine, CA, USA) is a system that uses a complex algorithm analyzing arterial waveform to calculate SV, SVV, and CO. We assessed the feasibility of obtaining SV measurements with a portable echocardiogram and validated its accuracy with the FTV system in mechanically ventilated patients in our intensive care unit (ICU). Furthermore, we emphasized the importance of hemodynamic measurements and familiarity with critical care echocardiography for the intensivists. METHODS: Ten patients who were on mechanical ventilation were studied. A femoral arterial line was connected to the FTV system monitoring SV and CO. A portable echocardiogram (M-Turbo; Sonosite, Bothell, WA) was used to measure SV. CO was calculated by multiplying SV by heart rate. No patient had arrhythmia. We used biplane Simpson's method of discs to calculate SV in which subtraction of end-systolic volume from end-diastolic volume yields the SV. RESULTS: The comparison of simultaneous SV and CO measurements by echocardiography with FTV showed a strong correlation between the 2. (For SV, y = 0.9545x + 3.3, R (2) = 0.98 and for CO, y = 0.9104x + 7.7074, R (2) = 0.97). CONCLUSIONS: In our small cohort, the SV and CO measured by a portable echocardiogram (Sonosite M-Turbo) appears to be closely correlated with their respective values measured by FTV. Portable echocardiography is a reliable noninvasive tool for the hemodynamic assessment of the critically ill. Its results need further validation with gold standard measures in a larger cohort of patients. However, our results suggest portable echocardiography could be an attractive tool in assessment of different hemodynamic scenarios in the critically ill.

Intracoronary upregulation of platelet extracellular matrix metalloproteinase inducer (CD147) in coronary disease.

BACKGROUND: CD147, also known as extracellular matrix metalloproteinase inducer, is present on circulating platelets and leukocytes in patients with coronary disease and is implicated in atherogenesis, and plaque rupture. We investigated whether CD147 (platelet, leukocyte and soluble) is upregulated within the coronary circulation in patients with stable coronary disease, and whether CD147 levels are associated with coronary shear stress levels. METHODS: A total of 25 patients undergoing intervention of a single coronary lesion had blood sampled within the coronary (n=15) and peripheral circulation (n=10). Platelet and leukocyte CD147 expression was measured by flow cytometry. Soluble CD147 was measured by enzyme-linked immunosorbent assays. Shear stress was calculated using computational fluid dynamics analysis. The effect of shear on platelet CD147 expression in vitro was investigated using a cone-plate viscometer. RESULTS: Platelet CD147 was higher in the coronary sinus (CS) compared to femoral vein (mean ± SD fluorescence intensity: 3.1 ± 0.7 vs. 2.2 ± 0.5, p=0.01). There was a significant linear trend for increased platelet CD147 expression from the proximal artery to the distal artery, and subsequently to the CS (p=0.01), indicating trans-lesion and transmyocardial upregulation. There were no differences between the various sites for monocyte, granulocyte or soluble CD147 levels (all p=ns). Trans-lesion gradients of CD147 did not correlate with shear stress (all p=ns). Blood subjected to shear in vitro had higher levels of platelet P-selectin (p=0.04) but similar levels of platelet CD147 (p=0.46) compared to rested blood. CONCLUSION: Platelet CD147 expression is upregulated in the coronary circulation in patients with stable coronary disease, but its upregulation is independent of shear stress.