As crucial factors in blood clot formation, shear stress distribution and low flow zones are assessed in different central venous catheter tip designs by using a combined numeric and experimental approach. Computational Fluid Dynamics was validated with Particle Image Velocimetry by comparing simulated and measured velocities and shear strains in three designs of the blood withdrawing arterial lumen: cylindrical and with tip (1) cut straight, (2) cut at an angle, or (3) cut straight with a sleeve entrance. After validation, four additional designs were studied: (4) with two side holes and tip cut straight or (5) at an angle, (6) concentric lumens, and (7) Ash Split-based. In these seven designs, shear stress (SS), blood residence time (RT), and Platelet Lysis Index, which combines the influence of shear stress magnitude and exposure time, were simulated. Concentric catheter was discarded due to highly elevated SS. Ash Split-based design had elevated RT values in the distal tip zone as major inflow occurs through the most proximal side holes, but this is compensated by low average SS. A straight-cut tip and possibly two side holes are preferred when aiming at minimal SS and RT. These data may lead to more patent catheters.

Central venous catheters are widely used as a hemoaccess method for dialysis therapy. In this study, the performance parameters (velocities, pressure drop, shear rates, access recirculation) of the Niagara catheter are analyzed using computational fluid dynamics. Side holes are left open, closed, or reduced in size to assess the influence of this design feature. Initially the catheter is inserted in a tube which represents the vena cava. In the "arterial" luminal tip, wall shear rates over 20,000 s(-1) are common and peaks attain 55,000 s(-1) at a 300 mL/min blood flow rate. The presence of side holes appears to affect the location but not the level of these elevated shear rates. Halving their diameter causes elevated shear rates to appear in a more extended region with peaks up to 80,000 s(-1). Simulated recirculation percentage is nil in normal catheter use, but attains 30% with reversed catheter connections. The results of the tube model are compared to those of an anatomically realistic right atrium model, which was three-dimensionally reconstructed. It is concluded that most catheter's specific hemodynamic properties can be deduced from the tube model.

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Long-term culturing of primary porcine hepatocytes (PPH) inside the Academic Medical Center (AMC)-bioartificial liver is characterized by increased anaerobic glycolysis. Recommendations to increase oxygen availability were proposed in a previous numerical study and were experimentally evaluated in this study. Original bioreactors as well as new configuration bioreactors with 2.2-fold thinner nonwoven matrix and 2-fold more capillaries were loaded with PPHs and oxygenated with different gas oxygen pressures resulting in medium pO(2) (pO(2-med)) of either 135-150 mm Hg or 235-250 mm Hg. After 6 days culturing, new configuration bioreactors with pO(2-med )of 250 mm Hg showed significantly reduced anaerobic glycolysis, 60% higher liver-specific functions, and increased transcript levels of five liver-specific genes compared to the standard bioreactor cultures. Changed bioreactor configuration and increasing pO(2-med) contributed equally to these improvements. Histological examination demonstrated small differences in cell organization. In conclusion, higher metabolic stability and liver-specific functionality was achieved by enhanced oxygen availability based on a prior modeling concept.

Abstract-A numerical model to investigate fluid flow and oxygen (O 2 ) transport and consumption in the AMCBioartificial Liver (AMC-BAL) was developed and applied to two representative micro models of the AMC-BAL with two different gas capillary patterns, each combined with two proposed hepatocyte distributions. Parameter studies were performed on each configuration to gain insight in fluid flow, shear stress distribution and oxygen availability in the AMC-BAL. We assessed the function of the internal oxygenator, the effect of changes in hepatocyte oxygen consumption parameters in time and the effect of the change from an experimental to a clinical setting. In addition, different methodologies were studied to improve cellular oxygen availability, i.e. external oxygenation of culture medium, culture medium flow rate, culture gas oxygen content (pO 2 ) and the number of oxygenation capillaries. Standard operating conditions did not adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to maintain O 2 consumption at minimally 90% of maximal uptake rate. Cellular oxygen availability was optimized by increasing the number of gas capillaries and pO 2 of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and maximal shear stresses were low and not considered to be harmful. This information can be used to increase cellular efficiency and may ultimately lead to a more productive AMC-BAL.