Computational Evaluation of Dialysis Fluid Flow in Dialyzers With Variously Designed Jackets

Dialyzer performance strongly depends on the flow of blood and dialysis fluid as well as membrane performance. It is necessary, particularly to optimize dialysis fluid flow, to develop a highly efficient dialyzer. The objective of the present study is to evaluate by computational analysis the effects of dialyzer jacket baffle structure, taper angle, and taper length on dialysis fluid flow. We modeled 10 dialyzers of varying baffle angles (0, 30, 120, 240, and 360°) with and without tapers. We also modeled 30 dialyzers of varying taper lengths (0, 12.5, 25.0, and 50.0 mm) and angles (0, 2, 4, and 6°) based on technical data of APS-SA dialyzers having varying surface areas of 0.8, 1.5, and 2.5 m² (Rexeed). Dialysis fluid flow velocity was calculated by the finite element method. The taper part was divided into 10 sections of varying fluid resistances. A pressure of 0 Pa was set at the dialysis fluid outlet, and a dialysis fluid flow rate of 500 mL/min at the dialysis fluid inlet. Water was used as the dialysis fluid in the computational analysis. Results for dialysis fluid flow velocity of the modeled dialyzers indicate that taper design and a fully surrounded baffle are important in making the dialysis fluid flow into a hollow-fiber bundle easily and uniformly. However, dialysis fluid flow channeling occurred particularly at the outflowing part with dialyzers having larger taper lengths and angles. Optimum design of dialysis jacket structure is essential to optimizing dialysis fluid flow and to increasing dialyzer performance.     

Improvement of Hemocompatibility on a Cellulose Dialysis Membrane with a Novel Biomedical Polymer Having a Phospholipid Polar Group

Abstract: To improve surface hemocompatibility on cellulose hollow fibers for hemodialysis, newly designed hemocompatible polymers with a phospholipid polar group, 2–methacryloyloxyethyl phosphory[choline (MPC) polymers, were introduced on the surface through two different methods: direct grafting of MPC on the surface, or coating of a water–soluble cellulose grafted with MPC. The MPC was polymerized using cerium ion as an initiator in the cellulose hollow fibers, and the poly(MPC) chains were grafted directly on the surface. Another modification of the cellulose hollow fibers was attempted by coating them with a water–soluble graft copolymer composed of a poly(MPC) side chain and a cellulose backbone. The coating process from an aqueous solution of the graft copolymer was very convenient, and the graft copolymer on the surface was not detached even after water circulated into the hollow fibers. These cellulose hollow fibers modified with MPC polymers displayed excellent hemocompatibility such as prevention of blood cell adhesion and aggregation after contact with blood without an anticoagulant. The permeability of the hollow fibers did not decrease as a result of these modifications. From these results, it is clearly suggested that introduction of the MPC units was effective for improving the hemocompatibility of the hollow fibers for hemodialysis.     

Hemocompatibility in Hemodialysis and Erythropoietin Therapy

Abstract: Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S + II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.     

Hemocompatibility of a Miniaturized Extracorporeal Membrane Oxygenation and a Pumpless Interventional Lung Assist in Experimental Lung Injury

Extracorporeal membrane oxygenation (ECMO) is used for most severe acute respiratory distress syndrome cases in specialized centers. Hemocompatibility of devices depends on the size and modification of blood contacting surfaces as well as blood flow rates. An interventional lung assist using arteriovenous perfusion of a low-resistance oxygenator without a blood pump (Novalung, Hechingen, Germany) or a miniaturized ECMO with reduced filling volume and a diagonal blood pump (Deltastream, Medos AG, Stolberg, Germany) could optimize hemocompatibility. The aim of the study was to compare hemocompatibility with conventional ECMO. Female pigs were connected to extracorporeal circulation for 24 h after lavage induced lung injury (eight per group). Activation of coagulation and immune system as well as blood cell damage was measured. A P value <0.05 was considered significant. Plasmatic coagulation was slightly activated in all groups demonstrated by increased thrombin-anti-thrombin III-complex. No clinical signs of bleeding or thromboembolism occurred. Thrombelastography revealed decreased clotting capacities after miniaturized ECMO, probably due to significantly reduced platelet count. These resulted in reduced dosage of intravenous heparin. Scanning electron microscopy of oxygenator fibers showed significantly increased binding and shape change of platelets after interventional lung assist. In all groups, hemolysis remained negligible, indicated by low plasma hemoglobin concentration. Interleukin 8 and tumor necrosis factor-α concentration as well as leukocyte count remained unchanged. Both devices demonstrated adequate hemocompatibility for safe clinical application, although a missing blood pump did not increase hemocompatibility. Further studies seem necessary to analyze the influence of different blood pumps on platelet drop systematically.     

Hemocompatibility Assessment of Carbonic Anhydrase Modified Hollow Fiber Membranes for Artificial Lungs

Hollow fiber membrane (HFM)‐based artificial lungs can require a large blood‐contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO₂) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO₂ toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM‐based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO₂ toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However, HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO₂ transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM‐based artificial lung.     

Clinical Evaluation of a New Water Removal Measuring Device in Standard Dialysis

A new device measuring water removal during standard dialysis is evaluated. The filtrate, collected from a small hemofilter inserted into a normal Cuprophan hollow-fiber dialyzer, was used to evaluate the total water removed from the patient. The device was tested in 46 patients undergoing regular dialysis treatment; the body weight loss ranged from 300 to 5,600 ml for a total of 71 dialysis sessions. Results confirmed the reliability of the device, as the mean prediction error was 5.4%. No influence of the dialyzer blood rest volume on the prediction error was observed. The authors propose this system as an alternative to bed or armchair scales and emphasize its usefulness for experimental purposes.     

Fatigue and Hemocompatibility of Polymer Materials

Hemocompatibility and sufficient fatigue life of biomaterials are critical in the development of artificial hearts and circulatory assist devices. In this study, three segmented polyurethanes (PUs) were compared with a fourth PU (Czech PU) and the organosilicone rubber RKM to determine the interrelationships between type of synthetic polymer, degree of structural change in cyclic loading, and hemocompatibility. Uniaxial and biaxial static strain tests were conducted. Accelerated fatigue tests were used to predict the behavior of the materials in vivo. Damage from fatigue was assessed by light transmission and light scattering methods, and the number of adhering platelets and degree of morphological change in the platelets were compared between initial and fatigued materials. The relative index of platelet adhesion and the relative form factor were also obtained. The elasticity characteristics of the PUs were shown to be substantially greater than those of RKM. RKM required reinforcement. Czech PU was shown to have good mechanical characteristics (with high elasticity and low creep). The morphology of the cells after cyclic load changed insignificantly, whereas the number of adherent platelets increased in all cases.     

Dialysis in Rats with Acute Renal Failure: Evaluation of Three Different Dialyzer Membranes

Abstract: Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure (ARF). To test this hypothesis, male Sprague-Dawley rats were allocated to 2 groups: in Group t, ARF was induced by bilateral renal artery clamping whereas in Group 2, animals underwent a sham procedure. In each group, rats were further allocated to undergo hemodialysis with either a Cu-prophan, a Hemophan, or a polyacrylonitrile minidialyzer on Days 4 and 8 after surgery, or no dialysis. Renal function was measured by inulin clearance on the days after dialysis. Additionally, total complement activity (CH₅₀) was estimated on Days 1, 2, 4, and 8, and complement factor C3 was detected immunohistochemically. The degree of renal failure and the rate of recovery of renal function were similar in all the ARF groups irrespective of whether they had undergone dialysis or not, or of the type of the dialysis membrane. Furthermore, there were no significant differences in the course of CH₅₀ or in the amount and distribution of complement factor C3 in the kidney tissue between the rats of Groups 1 and 2. Our findings refute the hypothesis that in ischemic ARF exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function in rats.     

Considerations on Developmental Aspects of Biocompatible Dialysis Membranes

Abstract: Modern strategies in developing new polymers for dialysis membranes aim to improve their blood compatibility. To achieve such a goal, two approaches have been successfully applied: existing cellulosic polymers were modified, either by introducing functional groups through ester or ether bonds, by mixing synthetic polymers with bulk additives, or by using copolymerization techniques. As a detailed example, the first synthetically modified cellulose membrane, Hemophan, was prepared by substituting some hydrogen atoms in the cellulosic glucose unit by diethyl-amino-ethyl groups with the modification having a considerable impact on the membrane's hemocompatibility. It is further known that the hemo-compatibility of hydrophobic synthetic membranes is improved by rendering these materials partially hydrophilic. We tested the hypothesis, whether the hemocompatibility of a material, which is hydrophilic per se, such as unmodified cellulose, is changed after the introduction of hydro-phobic substituents. For this purpose, the number and nature of substituents have been systematically varied in order to alter surface properties, and these variations have been subsequently related to blood compatibility parameters. As expected, thrombin generation as well as complement- and cell-activation depend on the number and nature of the substituents whereby some of the substituents show a very narrow optimum if their hemocompatibility is related to the degree of substitution. Changes in hemocompatibility can be followed by physical methods, such as surface angle analyses and zeta potential determinations. Data show that alterations in the li-pophilic/hydrophilic balance on the polymer surface may explain substituent-related changes in polymer hemocompatibility. Molecular modeling of membrane surface and protein structures may be of further help in understanding possible interactions. The recent conclusion is that polymer modification and techniques in membrane surface characterization help us to optimize membrane fabrication for specific applications.     

Adsorption of Complement, Cytokines, and Proteins by Different Dialysis Membrane Materials: Evaluation by Confocal Laser Scanning Fluorescence Microscopy

The membranes tested in the present study were cellulose triacetate (CTA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN). The adsorption by each membrane of albumin, IgG, C3a, interleukin-1β (IL-1β), interleukin-6 (IL-6), human neutrophil elastase (HNE), and tumor necrosis factor α (TNFα) was examined and semiquantitatively graded by confocal laser scanning fluorescence microscopy (CLSFM). After clinical use the dialyzers were treated with antibodies for these proteins and cytokines. Then the samples were incubated with fluorescein isothiocyanate-labeled anti-IgG antibody and observed by CLSFM. The changes in the blood levels of C3a and cytokines were also studied. In the CTA membrane, the adsorption of these substances, except for albumin and HNE, was less than in the synthetic membranes. The PAN membrane revealed the most abundant adsorption, especially for IL-1β, IL-6, and TNFα. Although a marked elevation of C3a in the blood was observed in the CTA membrane, considerable adsorption was evident in the PMMA and the PAN membranes. Because the changes in the blood levels could be affected by membrane adsorption, both the blood levels and the adsorption of the biocompatibility parameters should be evaluated when membrane biocompatibility is discussed.     

Hemocompatible Cellulose Dialysis Membranes Modified with Phospholipid Polymers

Abstract: Hemocompatibility is one of the most important properties for hemodialysis membranes. For improvement of the hemocompatibility on a cellulose dialysis membrane, modifications with new blood-compatible phospholipid polymers were carried out. These methods included a direct grafting of the phospholipid monomer on the membrane surface, coaling the membrane surface with a water-soluble graft copolymer composed of a cellulose backbone and phospholipid polymer as a branch, and covalent bonding with a reactive phospholipid polymer on the membrane surface. These modified membranes could reduce protein adsorption as well as complement activation and platelet adhesion on the surface without any adverse effects on the membrane performance.     

Effects of a Vitamin E-Modified Dialysis Membrane and Vitamin C Infusion on Oxidative Stress in Hemodialysis Patients

Hemodialysis deteriorates oxidative stress. Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane (E), nonmodified cellulose membrane (O), and vitamin C infusion (500 mg, C) into the arterial blood line during dialysis on parameters of oxidative stress. In a short-term study, 24 patients were subjected to a single dialysis session with E, O, E with C, and O with C protocols. In a long-term study (12 weeks), 20 patients were randomized into groups with C and without C on each dialysis, and both groups had dialysis using O, E, and again O membrane for 4 weeks each. In the short-term study, thiobarbituric acid reacting substances (TBARS) in plasma rose after dialysis (p < 0.02) with O, and no changes were observed in the other 3 protocols. In the long-term study, predialysis TBARS declined when using E both in the groups with C (p < 0.02) and without C (p < 0.05). A switch over to O resulted in TBARS returning to baseline levels. The E membrane prevented an increase in lipid peroxidation during single dialysis, and long-term use of the E membrane also resulted in a decrease in the predialysis lipid peroxidation level. The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion. High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation, most probably due to the enhanced rate of endogenous vitamin E regeneration.     

Fabrication,Characterization, and Hemocompatibility Investigation of Polysulfone Grafted With Polyethylene Glycol and Heparin Used in Membrane Oxygenators

Polysulfone (PSF) was grafted chemically with polyethylene glycol (PEG) of different molecular weights (400, 2000, 10 000, and 20 000) and heparin to prepare PSF–PEG–Hep membranes (labeled as PSF–PEG400–Hep, PSF–PEG2000–Hep, PSF–PEG10 000–Hep, and PSF–PEG20 000–Hep). These membranes were synthesized via the following steps: (i) PSF chloromethylation; (ii) PEGylation; and (iii) heparin immobilization process. Water contact angle, critical water permeation pressure, ATR–FTIR, ¹H NMR, UV–visible spectrophotometry, and X‐ray photoelectron spectroscopy were conducted to prove grafting success and to fix the optimal reaction parameters during chemical modification processes. To further evaluate the application potential of the PSF–PEG–Hep membrane in a membrane oxygenator, we conducted pure CO₂ and O₂ gas permeation tests and measured the gas exchange rates of CO₂ and O₂ through a membrane oxygenator using fresh porcine blood. Meanwhile, the hemocompatibility of the membrane was analyzed and compared by protein adsorption, platelet adhesion, and blood coagulation tests. Results of pure gas permeation experiments indicated that the excellent gas transmission properties through PSF membrane were preserved after modification. Blood oxygenation experiments through the PSF–PEG10 000–Hep membrane showed that when the flow rate of porcine blood was 1.5 L/min, CO₂ and O₂ exchange rates reached 102 and 110 mL/min, respectively, which could basically satisfy the gas exchange potential of commercial membrane oxygenators. Besides, the PSF–PEG–Hep membrane has demonstrated more prominent blood compatibility than PSF.     

Forward Osmosis Process for Dialysis Fluid Regeneration

In a preliminary experiment, 38% of the spent dialysis fluid water was reclaimed by a forward osmosis process through a cellulose triacetate membrane. The simplicity of forward osmosis and its minimal external energy requirements may allow the construction of a small bulk device that can reclaim a considerable portion of the water used in the patient's dialysis process. For developing an acceptable ambulatory dialysis system, decreasing the bulk of the fluid and equipment carried on the patient is essential. Forward osmosis may feasibly be used for dialysis fluid regeneration in ambulatory dialysis systems.     

Improvement of Hemocompatibility in Centrifugal Blood Pump With Hydrodynamic Bearings and Semi-open Impeller: In Vitro Evaluation

We have developed a noncontact-type centrifugal blood pump with hydrodynamic bearings and a semi-open impeller for mechanical circulatory assist. The impeller is levitated by an original spiral-groove thrust bearing and a herringbone-groove journal bearing, without any additional displacement-sensing module or additional complex control circuits. The pump was improved by optimizing the groove direction of the spiral-groove thrust bearing and the pull-up magnetic force between the rotor magnet and the stator coil against the impeller. To evaluate hemocompatibility, we conducted a levitation performance test and in vitro hemocompatibility tests by means of a mock-up circulation loop. In the hemolysis test, the normalized index of hemolysis was reduced from 0.721 to 0.0335 g/100 L corresponding to an expansion of the bearing gap from 1.1 to 56.1 µm. In the in vitro antithrombogenic test, blood pumps with a wide thrust bearing gap were effective in preventing thrombus formation. Through in vitro evaluation tests, we confirmed that hemocompatibility was improved by balancing the hydrodynamic fluid dynamics and magnetic forces.     

环氧交联去细胞牛颈静脉带瓣管道的血液相容性实验研究

目的评价环氧化合物（PC）交联去细胞牛颈静脉带瓣管道（BJVC）的血液相容性,探讨其在心血管外科和组织工程中的应用前景。方法选取本地健康杂种犬20只,采用随机数字表法分为实验组（n=10）和对照组（n=10）。实验组用PC交联的去细胞BJVC,对照组采用戊二醛（GA）交联的BJVC。运用兔血进行体外溶血实验计算溶血率,绘制时间-吸光度曲线;采用人全血测定D-二聚体和补体C3a des Arg水平评价其体外血液相容性。采用PC和GA制备的BJVC重建犬右心室-肺动脉连接,两组犬饲养10个月后,观察有无血栓形成评价其体内血液相容性。结果实验组溶血率（0.23%）低于对照组（0.35%）,符合医用生物材料的国家标准（〈5%）。实验组的凝血时间曲线较对照组平缓。实验组D-二聚体水平低于对照组,两组差异有统计学意义（0.10±0.01μg/ml vs.0.12±0.02μg/ml,t=3.277,P=0.004）,但均在正常范围内。实验组补体C3a des Arg水平低于对照组,两组差异有统计学意义（0.74±0.09μg/ml vs.1.02±0.19μg/ml,t=4.183,P=0.001）。犬右心室-肺动脉连接重建术后10个月每组各有8只生存,各有2只死于心室颤动。对照组3例有血栓形成,实验组无血栓形成。结论与GA交联相比,PC交联的BJVC体外、体内血液相容性均具优势,临床应用前景良好。     

层层自组装肝素/胶原复合涂层聚四氟乙烯小口径人工血管的研究

目的 观察层层自组装肝素/胶原复合涂层聚四氟乙烯小口径人工血管片的抗凝血性能和血液相容性.方法 实验分为复合人工血管片组和普通人工血管片组.采用层层静电组装的方法将带负电的肝素与带正电的胶原交替涂覆到聚四氟乙烯小口径人工血管片上,制备成复合人工血管片.参照IS010993-4及GB/TI6886标准中实验方法行血小板黏附实验、溶血实验及血浆复钙时间实验检测.结果 扫面电镜照片可以观察到普通人工血管片表面有大量血小板黏附,血小板呈扁平状贴覆在材料表面,复合血管片组表面有少量血小板贴覆(2.5±2.4比28.5±4.8,P＜0.05);普通血管片溶血率0.63％,复合血管片溶血率1.27％,均＜5％,且两者差异无统计学意义(P＞0.05);普通血管片血浆复钙时间为8.5 min,复合血管片观察至30 min未见纤维蛋白丝.结论 层层自组装肝素/胶原复合涂层聚四氟乙烯小口径人工血管片具有良好的抗凝血性能及血液相容性.     

Respiratory Gas Exchange Through the Hydrophilic Membrane

To assess the efficiency of respiratory gas exchange in vitro through a dialysis membrane mounted inside a flat plate Kiil dialyzer, the model reactions of hydrogen peroxide reduction by a metal ion and of the carbon dioxide precipitation in the form of a carbonate in the dialysate were used. A comparison of the rates of oxygen output obtained for a membrane fixed in the test chamber and those for a membrane inside the dialyzer showed that the performance of the membrane as an oxygen source in the latter arrangement is much poorer than that in the former one. This was attributed to the inadequate dialysate channel geometry of the dialyzer with respect to the catalytic reaction. However, the dialyzer geometry did not impede a quick removal of carbon dioxide. Washout of the catalyst (cobalt oxide) was observed. Hydrogen peroxide leakage to the blood side of the membrane was negligible.     

Modification of the Harris Hip Score in acetabular fracture treatment

The aim of this study was to adjust the Harris Hip Score for evaluation of acetabular fracture treatment. The discriminating quality of the score was assessed. As there was low discriminating capacity at the upper end of the scale, with a high ceiling effect and the 60th percentile showing top points, the score was modified and re-evaluated. The discrimination of the modified score was improved, with the 90th percentile giving top points. Differences in treatment outcome of acetabular fractures will be easier to detect with the modified score.