Flow-Mediated Drug Transport from Drug-Eluting Stents is Negligible: Numerical and In-vitro Investigations.

Prior numerical studies have shown that the blood flow patterns surrounding drug-eluting stents can enhance drug uptake in stented arteries. However, these studies employed steady-state simulations, wherein flow and drug transport parameters remained constant with respect to time. In the present study, numerical simulations and in-vitro experiments were performed to determine whether luminal blood flow patterns can truly enhance drug uptake in stented arteries. Unlike the aforementioned studies, the time-varying depletion of drug within the stent coating was modelled and the simulation results were validated qualitatively with the in-vitro experiments. The simulations showed that the non-Newtonian properties of blood, its complex near-wall behavior, and the pulsatility of its flow all affect drug uptake only modestly. Furthermore, flow-mediated drug transport was found to be negligible due to the rapid rate at which drug depletes at the stent coating surfaces that are exposed to arterial blood flow. For fluid dynamicists, these results show that steady-state simulations must be avoided when modelling drug transport in stented arteries. For device designers, these results may be used to optimize the shape of drug-eluting stent struts and coatings to improve stent efficacy.

The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations.

BACKGROUND AND METHODS: It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood's complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates. RESULTS: Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection. CONCLUSIONS/SIGNIFICANCE: These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers.

Two-dimensional computational analysis of microbubbles in hemodialysis.

On average, an end-stage renal disease patient will undergo hemodialysis (HD) three or four times a week for 4-5 h per session. Any minor imperfection in the extracorporeal system may become significant in the treatment of these patients due to the cumulative exposure time. Recently, air traps (a safety feature of dialysis systems) have been reported to be inadequate in detecting microbubbles and may even create them. Microbubbles have been linked to lung injuries and damage to the brain in chronic HD patients; therefore the significance of microbubbles has been revisited. Bubbles may originate at the vascular access sites, sites of local turbulent blood flow, the air trap, or in the bloodlines after priming with saline prior to use. In this paper, computational fluid dynamics is used to model blood flow in the air trap to determine the likely mechanisms of microbubble dynamics. The results indicate that almost all bubbles with diameters less than 50 µm and most of the bubbles of 50-200 µm pass through the air trap. Consequently, the common air traps are not effective in removing bubbles less than 200 µm in diameter.

Parameter-optimized model of cardiovascular-rotary blood pump interactions.

A lumped parameter model of human cardiovascular-implantable rotary blood pump (iRBP) interaction has been developed based on experimental data recorded in two healthy pigs with the iRBP in situ. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, as well as the iRBP. A subset of parameters was optimized in a least squares sense to faithfully reproduce the experimental measurements (pressures, flows and pump variables). Our fitted model compares favorably with our experimental measurements at a range of pump operating points. Furthermore, we have also suggested the importance of various model features, such as the curvilinearity of the end systolic pressure-volume relationship, the Starling resistance, the suction resistance, the effect of respiration, as well as the influence of the pump inflow and outflow cannulae. Alterations of model parameters were done to investigate the circulatory response to rotary blood pump assistance under heart failure conditions. The present model provides a valuable tool for experiment designs, as well as a platform to aid in the development and evaluation of robust physiological pump control algorithms.

Noninvasive average flow and differential pressure estimation for an implantable rotary blood pump using dimensional analysis.

Accurate noninvasive average flow and differential pressure estimation of implantable rotary blood pumps (IRBPs) is an important practical element for their physiological control. While most attempts at developing flow and differential pressure estimate models have involved purely empirical techniques, dimensional analysis utilizes theoretical principles of fluid mechanics that provides valuable insights into parameter relationships. Based on data obtained from a steady flow mock loop under a wide range of pump operating points and fluid viscosities, flow and differential pressure estimate models were thus obtained using dimensional analysis. The algorithm was then validated using data from two other VentrAssist IRBPs. Linear correlations between estimated and measured pump flow over a flow range of 0.5 to 8.0 L/min resulted in a slope of 0.98 ( R(2) = 0.9848). The average flow error was 0.20 +/- 0.14 L/min (mean +/- standard deviation) and the average percentage error was 5.79%. Similarly, linear correlations between estimated and measured pump differential pressure resulted in a slope of 1.027 ( R(2) = 0.997) over a pressure range of 60 to 180 mmHg. The average differential pressure error was 1.84 +/- 1.54 mmHg and the average percentage error was 1.51%.

A dynamic lumped parameter model of the left ventricular assisted circulation.

A lumped parameter model of the cardiovascular system (CVS) and its interaction with an implantable rotary blood pump (iRBP) is presented. The CVS model consists of the heart, the systemic and the pulmonary circulations. The pump model is made up of three differential equations, i.e. the motor equation, the torque equation and the hydraulic equation. Qualitative comparison with data from ex vivo porcine experiments suggests that the model is able to simulate different physiologically significant pumping states with varying pump speed set points. The combined CVS-iRBP model is suitable for use as a tool for investigating changes in the circulatory system parameters in the presence of the pump, and for testing control algorithms.