Association between triglyceride and high-density lipoprotein cholesterol change following fibrate therapy.

BACKGROUND: Debate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels. METHODS: Data was collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG. RESULTS: Multiple regression analysis revealed that TG change was associated with pre-treatment TG (p<0.001) and TC levels (p=0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels. CONCLUSIONS: The actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.

Multi-scale interaction of particulate flow and the artery wall.

We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a continuum fluid), and proceed to propose, then validate all the key components in a multiply-coupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state.

Numerical model for the investigation of dual-flow in a spiral counter-current chromatography column.

In dual-flow counter-current chromatography (DF-CCC), the two immiscible liquids are flowing in opposite directions in the coil. The method allows for the continuous separation of two solutes. In this study a numerical model was developed to allow for the detailed investigation of flow in such columns. The mesh model of the presented DF spiral column was developed in line with an existing experimental model. The paper presents results during the early filling stages for different rotation directions. These clearly illustrate the performance of the developed model by (1) confirming the importance of flowing the lighter phase from tail to head and the heavier phase from head to tail and (2) by visualising mixing waves and the recognised back and forth "swish-swash" motion as present in CCC in that operating mode.

Flow mixing and fluid residence times in a model of a ventricular assist device.

To provide a reliable tool for predicting the flow in a clinical sac-type ventricular assist device (VAD), a simplified model VAD was developed prior to this study for the purpose of experimental validation of computer simulations of the time-varying flow on a moving grid. At selected locations in the flow field, flow patterns, vortex core trajectories and velocities were compared between the numerical and physical models during one full pumping cycle. The computer simulations showed qualitatively very good agreement with the experiment. Quantitatively, the agreement was less favourable. In order to investigate flow mixing and to evaluate fluid residence times in the model VAD a new tool has been developed: the numerical simulations were extended by injecting a scalar into the flow domain. These simulations allow investigation of the flow mixing qualitatively by visualisation and quantification of fluid residence times. Experimental assessment of the numerical results using dye injection proved to be favourable. The numerical results have been extended to include some prediction of pressure which have been compared with experimental measurements.

Comparison of flow in numerical and physical models of a ventricular assist device using low- and high-viscosity fluids.

The flows in a model of a ventricular assist device (VAD) were investigated numerically and experimentally for two different Newtonian test fluids. These were a blood analogue fluid and a much higher viscosity fluid. A finite volume method was employed to solve the governing equations for a three-dimensional unsteady laminar flow on a transient grid. The numerical solutions were compared with experimental results from an identical physical model. The experimental flows were investigated by flow visualization and by laser Doppler velocity measurements at selected points in the flow field. The validation was based on comparisons of flow patterns and of non-component velocity-time histories. The maximum Reynolds numbers in the inflow tube of the model VAD were approximately 460 and 3300 using the high- and low-viscosity fluids respectively. The investigation showed that the flow patterns were better predicted for the high-viscosity fluid. However, the agreement between the velocity-time histories was found to be slightly better for the low-viscosity fluid. The discrepancies in the flow patterns may be due to intermittent turbulence with a further contribution from numerical diffusion.

Investigation of unsteady flow in a model of a ventricular assist device by numerical modelling and comparison with experiment.

Prior to this study, a clinical prototype of a sac-type ventricular assist device (VAD) was investigated experimentally, using both flow visualisation and Laser Doppler anemometry (LDA), in order to optimise its geometry. As poor optical access precluded the experimental investigation of the flow in some areas of the prototype VAD, computational fluid dynamics (CFD) was used in the present work. Flow patterns during one full pumping cycle were investigated in a simplified model of the VAD. The numerical solutions were compared with experimental results from an identical physical model. The model consists of the hemispherical cylinder and two attached tubes for the inflow and outflow. Instead of a diaphragm in the clinical device, which deforms non-uniformly during pumping, a piston with a matching hemispherical crown was used. A finite volume method was employed to solve the governing equations for the three-dimensional, unsteady, laminar flow of an incompressible, Newtonian fluid. The general flow features were predicted very well by the simulation, with some differences in the details of the flow structures. This allows the conclusion that CFD can be used to facilitate improvement of the design of the clinical device. The comparison of one-component velocity time histories at selected points showed that the predicted velocities were approximately 20-50% lower than those measured by LDA. Such underprediction would lead to erroneous results for particle residence times and may result in an underestimation of wall shear stresses.