Computational assessment of the effects of a pulsatile pump on toxin removal in blood purification

<p>Abstract</p> <p>Background</p> <p>For blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods.</p> <p>Methods</p> <p>We devised a new mathematical lumped model to assess the toxin removal efficiency of blood purification systems in patients, integrating the mass transfer model for a human body with a dialyser. The human body model consists of a three-compartment model of body fluid dynamics and a two-compartment model of body solute kinetics. We simulated three types of blood purification therapy with the model, hemofiltration, hemodiafiltration, and high-flux dialysis, and compared the simulation results in terms of toxin (urea and beta-2 microglobulin) clearance and the treatment dose delivered under conditions of pulsatile and non-pulsatile pumping. <it>In vivo </it>experiments were also performed to verify the model results.</p> <p>Results</p> <p>Simulation results revealed that pulsatile flow improved the convective clearance of the dialyser and delivered treatment dose for all three types of therapy. Compared with the non-pulsatile pumping method, the increases in the clearance of urea and beta-2 microglobulin with pulsatile pumping were highest with hemofiltration treatment (122.7% and 122.7%, respectively), followed by hemodiafiltration (3.6% and 8.3%, respectively), and high-flux dialysis (1.9% and 4.7%, respectively). EKRc and std Kt/V averaged 28% and 23% higher, respectively, in the pulsatile group than in the non-pulsatile group with hemofiltration treatment.</p> <p>Conclusions</p> <p>The pulsatile effect was highly advantageous for all of the toxins in the hemofiltration treatment and for β₂-microglobulin in the hemodiafiltration and high-flux dialysis treatments.</p

Computational Analysis of Cardiovascular Hemodynamics

The human body requires a complex circulatory system to supply nutrients to, and to remove metabolic waste products from, its tissues. Given this primary purpose, circulatory function is closely related to the hemodynamic characteristics of blood vessels. This includes not only macroscale fluid dynamics, but also mass transfer in the microvasculature. Many experimental and clinical studies have examined these characteristics of vascular function. Over the past 50 years, mathematical modeling has become a powerful adjunct to such studies, as modeling provides a rational framework within which to analyze the cardiovascular system

The three-dimensionality of the hiPSC-CM spheroid contributes to the variability of the field potential

Background: Field potential (FP) signals from human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) spheroid which are used for drug safety tests in the preclinical stage are different from action potential (AP) signals and require working knowledge of the multi-electrode array (MEA) system. In this study, we developed in silico three-dimensional (3-D) models of hiPSC-CM spheroids for the simulation of field potential measurement. We compared our model simulation results against in vitro experimental data under the effect of drugs E-4031 and nifedipine.Methods:In silico 3-D models of hiPSC-CM spheroids were constructed in spherical and discoidal shapes. Tetrahedral meshes were generated inside the models, and the propagation of the action potential in the model was obtained by numerically solving the monodomain reaction-diffusion equation. An electrical model of electrode was constructed and FPs were calculated using the extracellular potentials from the AP propagations. The effects of drugs were simulated by matching the simulation results with in vitro experimental data.Results: The simulated FPs from the 3-D models of hiPSC-CM spheroids exhibited highly variable shapes depending on the stimulation and measurement locations. The values of the IC50 of E-4031 and nifedipine calculated by matching the simulated FP durations with in vitro experimental data were in line with the experimentally measured ones reported in the literature.Conclusion: The 3-D in silico models of hiPSC-CM spheroids generated highly variable FPs similar to those observed in in vitro experiments. The in silico model has the potential to complement the interpretation of the FP signals obtained from in vitro experiments

Prediction of Plaque Progression in Coronary Arteries Based on a Novel Hemodynamic Index Calculated From Virtual Stenosis Method

RationalePredicting the sites in coronary arteries that are susceptible to plaque deposition is essential for the development of clinical treatment strategies and prevention. However, to date, no physiological biomarkers for this purpose have been developed. We hypothesized that the possibility of plaque deposition at a specific site in the coronary artery is associated with wall shear stress (WSS) and fractional flow reserve (FFR).Background and ObjectiveWe proposed a new biomarker called the stenosis susceptibility index (SSI) using the FFR and WSS derived using virtual stenosis method. To validate the clinical efficacy of this index, we applied the method to actual pilot clinical cases. This index non-invasively quantifies the vasodilation effects of vascular endothelial cells relative to FFR variation at a specific coronary artery site.Methods and ResultsUsing virtual stenosis method, we computed maximum WSS and FFR according to the variation in stenotic severity at each potential stenotic site and then plotted the variations of maximum WSS (y-axis) and FFR (x-axis). The slope of the graph indicated a site-specific SSI value. Then we determined the most susceptible sites for plaque deposition by comparing SSI values between the potential sites. Applying this method to seven patients revealed 71.4% in per-patient basis analysis 77.8% accuracy in per-vessel basis analysis in percutaneous coronary intervention (PCI) site prediction.ConclusionThe SSI index can be used as a predictive biomarker to identify plaque deposition sites. Patients with relatively smaller SSI values also had a higher tendency for myocardial infarction. In conclusion, sites susceptible to plaque deposition can be identified using the SSI index

Theoretical Estimation of Cannulation Methods for Left Ventricular Assist Device Support as a Bridge to Recovery

Left ventricular assist device (LVAD) support under cannulation connected from the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart failure patients because it is non-invasive to ventricular muscle. However, it has serious problems, such as valve stenosis and blood thrombosis due to the low ejection fraction of the ventricle. We theoretically estimated the effect of the in-series cannulation, connected from ascending aorta to descending aorta (AA-DA), on ventricular unloading as an alternative to the LA-AA method. We developed a theoretical model of a LVAD-implanted cardiovascular system that included coronary circulation. Using this model, we compared hemodynamic responses according to various cannulation methods such as LA-AA, AA-DA, and a cannulation connected from the left ventricle to ascending aorta (LV-AA), under continuous and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left ventricular peak pressure than the LA-AA method under continuous and pulsatile LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing ventricular unloading whereas the AA-DA method is a better choice to increase coronary perfusion

Computational Analysis of Tumor Angiogenesis Patterns Using a Two-dimensional Model

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface