We systematically analyzed the relative contributions of frequency component elements of hemodynamic shear stress waveforms encountered in cardiovascular blood recirculating devices as to overall platelet activation over time. We demonstrated that high frequency oscillations are the major determinants for priming, triggering and yielding activated “prothrombotic behavior” for stimulated platelets, even if the imparted shear stress has low magnitude and brief exposure time. Conversely, the low frequency components of the stress signal, with limited oscillations over time, did not induce significant activation, despite being of high magnitude and/or exposure time. In vitro data were compared with numerical predictions computed according to a recently proposed numerical model of shear-mediated platelet activation. The numerical model effectively resolved the correlation between platelet activation and the various frequency components examined. However, numerical predictions exhibited a different activation trend compared to experimental results for different time points of a stress activation sequence. With this study we provide a more fundamental understanding for the mechanobiological responsiveness of circulating platelets to the hemodynamic environment of cardiovascular devices, and the importance of these environments in mediating life-threatening thromboembolic complications associated with shear-mediated platelet activation. Experimental data will guide further optimization of the thromboresistance of cardiovascular implantable therapeutic devices.

The potential of convective solute transport for blood purification has been widely explored. New techniques (such as hemodiafiltration), based on a combination of diffusion and convection techniques, have been developed. Owing to the internal filtration/backfiltration (IF/BF) phenomenon, high-flux dialysis also relies on a convective component, which, however, is hard to quantify and thus optimize. In this work, we developed a mathematical model designed to supply the clinician with a quantification of the IF/BF fluxes taking place during high-flux dialysis. IF fluxes are predicted based on the machine settings and blood hematocrit/protein concentration. The hydraulic characteristics of commercial dialyzers were derived from bloodless bench tests. Moreover, an in vitro blood test was conducted on a 1.8 m² polysulfone dialyzer using an established scintigraphic analysis, for verification of model prediction accuracy. Results of simulations show that the IF/BF rate is sensitive to the blood flow rate and (to a lesser extent) to the dialysate flow rate. Increasing net ultrafiltration rates resulted in parallel increases of direct filtration and simultaneous decreases of BF. IF/BF is rather influenced by blood composition, due to the complex dependence of oncotic pressure and blood viscosity upon hematocrit and plasma protein concentration. Simulation results showed an excellent agreement with the experimental results obtained with scintigraphy, with only a 3% prediction error. With respect to some previous works, this model is simpler in its theoretical approach. It allows implementation into a user-friendly software tool and might be used to predict the convective component in high-flux dialysis and possibly to optimize it.

Gaseous embolism is still a concern in cardiopulmonary bypass, and the use of arterial line filters (ALFs) is widespread because of their recognized role in increasing safety. Currently, the methods used for the optimization/evaluation of ALF designs are based on a trial-and-error approach. In this work, we propose a method to objectively assess the air-handling capabilities of ALFs, using computational fluid dynamics (CFD) simulations to track the trajectory of large numbers of bubbles traversing the device under examination. We applied the CFD method to ALF prototypes, whose design featured the classical purge/screen configuration, to establish the relative roles of the bubble-trap and bubble-barrier deairing effects. Simulations were run at the maximum rated blood flows. Clusters of hundred bubbles in the micro- to macroembolic size range (10–1,000 μm diameter) were tracked. The results quantified the relative amount of bubbles whose fate is either to reach the purge line or to be intercepted by the filter screen. For microbubbles, the analysis detailed how the screen barrier is exploited, mapping the percent distribution of the intercepted bubbles along the screen surface. We conclude that the method proposed increases knowledge and awareness in designing an optimal exploitation of the filtration mechanisms involved in ALFs.

Extracorporeal endotoxin removal by means of the Toraymyxin device is based on the ability of polymyxin B to bind endotoxins with a high specificity. The endotoxins/polymyxin molecular interactions were computationally analyzed in a parallel work (Part I). In this paper we investigate with a multi-scale approach the phenomena involving blood and plasma fluid dynamics inside the device. The macro- and mesoscale phenomena were studied by means of 3D models using computational fluid dynamics. The flow behavior in the sorbent material was focused, modeling the sorbent as a homogeneous porous medium at the macroscale level, or accounting for the realistic geometry of its knitted fibers at the mesoscale level. A microscale model was then developed to analyze the behavior of endotoxin molecules subjected to the competition of flow drag and molecular attraction by fibergrafted polymyxin B. The macroscale results showed that a very regular flow field develops in the sorbent, furthermore supplying the peak velocity to be input in the lower-scale model. The mesoscale analysis yielded the realistic range for wall shear stresses (WSSs) acting on fiber walls. With WSS values in the entire range, the results of the microscale analysis demonstrated that the capability of polymyxin B to capture endotoxin molecules from the flow extends at distances one order of magnitude greater than the characteristic distance of the stable intermolecular bond. We conclude that the use of an integrated, multi-scale analysis allows for a comprehensive understanding of the complex mechanisms involved in endotoxin sorption phenomena with immobilized polymyxin B.

The relationship between extracranial venous system abnormalities and central nervous system disorders has been recently theorized. In this paper we delve into this hypothesis by modeling the venous drainage in brain and spinal column areas and simulating the intracranial flow changes due to extracranial morphological stenoses. A lumped parameter model of the cerebro-spinal venous drainage was created based on anatomical knowledge and vessels diameters and lengths taken from literature. Each vein was modeled as a hydraulic resistance, calculated through Poiseuille’s law. The inputs of the model were arterial flow rates of the intracranial, vertebral and lumbar districts. The effects of the obstruction of the main venous outflows were simulated. A database comprising 112 Multiple Sclerosis patients (Male/Female = 42/70; median age ± standard deviation = 43.7 ± 10.5 years) was retrospectively analyzed. The flow rate of the main veins estimated with the model was similar to the measures of 21 healthy controls (Male/Female = 10/11; mean age ± standard deviation = 31 ± 11 years), obtained with a 1.5 T Magnetic Resonance scanner. The intracranial reflux topography predicted with the model in cases of internal jugular vein diameter reduction was similar to those observed in the patients with internal jugular vein obstacles. The proposed model can predict physiological and pathological behaviors with good fidelity. Despite the simplifications introduced in cerebrospinal venous circulation modeling, the key anatomical feature of the lumped parameter model allowed for a detailed analysis of the consequences of extracranial venous impairments on intracranial pressure and hemodynamics.