The International Journal of Artificial Organs

Although it has been suggested that pulmonary sequestration of leukocytes could account for membrane-dependent white blood cell depletion in HD, direct evidence in patients is still lacking. Therefore a study was initiated to test whether and how leukocytes distribute in the lung circulation during HD with different membranes. Thirteen patients suffering from chronic renal failure underwent lung scintigraphy during HD with cuprophane (n = 3), hemophane (n = 8) and polysulfone (n = 2) lowflux capillary dialyzers. Isolated autologous leukocytes were labelled with 99m-Technetium and reinfused before starting HD. Distribution of leukocyte related activity was registered by lung scintigraphy. In comparison to normal lung scintigraphy performed without HD, an impressive redistribution peak was demonstrated 10-20 min after the start of HD with cuprophane and also to a lesser extent with hemophane. When HD was performed with polysulfone the decrease in activity was delayed but no real redistribution was obtained.

In accordance with other phenomena, such as peripheral leukopenia and changes in granulocyte oxidative metabolism, pulmonary sequestration of leukocytes takes place in man in the initial phase of HD and appears to be strongly dependent on the type of membrane. (Int J Artif Organs 1990; 13: 729-36)

To define the prevalence of non-A, non-B hepatitis, antibodies to HCV were detected in 193 patients on renal replacement therapy (52 transplant and 141 hemodialysis patients) and in 50 staff members of a Nephrology Department. Unequivocal seroconversion was documented in 5 transplant (9.6%) and in 26 dialysis patients (18.4%). In the dialysis population, the prevalence of anti-HCV antibodies was evaluated in patients grouped according to the number of blood transfusions and to the different sections of dialytic treatment. The most striking findings were the marked differences in the prevalence of anti-HCV antibodies among patients treated in different sections (from 0% to 70%), and the presence of a significant increase in alanine-amino-transferase (ALT) concentrations in 14 anti-HCV negative patients. The results suggest that the diffusion of non-A, non-B hepatitis is mainly transfusion-related, with the possibility of significant environmental diffusion related to the violation of infection-control measures. The current immunoassay is probably unable to detect the actual frequency of the infection.

Accounting for the non-Newtonian blood viscosity by the Quemada descriptive viscosity equation, we deduced velocity profiles and volumetric capillary flows from the Navier-Stokes-equation. An arbitrary axial and/or radial hematocrit profile can be chosen. The hematocrit dependence of the intrinsic viscosities k_o (H) (characterizing, at least in part, the RBC aggregation) and k_∞ (H) (describing orientation/deformation of RBC) was taken into account.

Velocity profiles for pressure gradients of 4-4000 Pa/cm show a distinct flattening, if a pronounced axial migration of RBC is assumed. The higher the axial concentration, the higher the flow at the same pressure gradient. Small deviations (≤ 10%) of the capillary number per dialyzer or of the radius of capillaries lead to a strong change of the pressure gradient with the same dialyzer flow. Whereas small hydraulic conductivities do not significantly change this gradient, high conductivities decrease the pressure gradient by about 10%. Impaired blood flow properties (hemoconcentration) result in a slight deviation from the linear axial pressure drop.

The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.

The primary goal of the presented project was to develop a pump family with stroke volumes of 20, 50, 70 and 90 ml, which could be produced at low cost but with sufficient quality. The housing parts of the pump were thermoformed from technical semifinished materials. All blood contacting surfaces of the pump were coated with biomaterials in a controlled dipping process. During the design and fabrication process a professional CAD-system was used. This facilitated spatial presentations of pump components for first evaluations at the initial draft stages. The CAD-design data were then transformed to CNC-controlled lathes and mill's for the fabrication of pump tools. The stresses and strains of the moving blood pump components, such as membranes and valves, were precalculated by means of Finite-Element-Analysis (FEM).

After completion of the pump, the internal flow fields were investigated by flow-visualization techniques using non-Newtonian test fluids, and the pump characteristics (function curves) were investigated in appropriate circulatory mock loops.

The paper covers all above aspects from first draft to final fabrication and testing.

A therapeutic immunoadsorption system on immobilized and anti-apolipoprotein B as a plasma cholesterol lowering procedure was optimized. Several antibodies were compared and highest adsorption capacity was obtained with goat polyclonal antibodies. Optimum quantities of antibodies to be immobilized on the gel and quantities of apo-B to be applied to columns were determined. The amount of antibodies released from immunoadsorbents can be minimized by treatment with a 0.005% glutaraldehyde solution with an acceptable reduction rate of adsorption capacity. Each phase, adsorption and desorption respectively, were well-defined and synchronized so two columns could be used in parallel in an automated procedure.

In these conditions, the immunoadsorption system can efficiently, specifically and safely remove cholesterol and has to be subjected to clinical trials.

The effect of heparin or citrate anticoagulation on blood cellular, complement pathway and coagulation pathway was investigated in a membrane plasma exchange procedure. Two membrane plasma separators constructed of cellulose di-acetate (CA) and polyvinyl chloride (PVC) were evaluated with heparin or citrate alone for anticoagulation in a 26 year old male with myasthenia gravis. Maximum white blood cell counts decrease was 21% at 30 min for the CA with heparin while no decrease was observed for the other schemes. Platelet counts changes were comparable between heparin and citrate, while the PVC groups showed less changes than the CA groups. The CA groups, regardless of the type of anticoagulant used, indicated that complement activation occurred via the classical pathway within the module in addition to the activation via alternative pathway for the CA with heparin. In the PVC groups, complement activation was noted to occur only when heparin was used for anticoagulation. PT and PTT showed slight increases with citrate, while they were remarkably prolonged with heparin. Citrate showed less changes in cellular and humoral factors compared to heparin. CA with heparin was the most activating combination of membrane material and anticoagulant, while the PVC with citrate was the least activating combination.