Hemostatic Changes Induced In Vitro by Hemoperfusion Over Activated Charcoal

The effect of hemoperfusion over charcoal on changes in platelet counts, coagulation factor concentrations and standard coagulation tests were determined during a two-hour in vitro perfusion of normal blood through a column containing 20 gm of activated charcoal, either uncoated or coated with 0.5% acrylonitrile/dimethylaminoethyl methacrylate copolymer (AN/DMAEMA). With citrated whole blood, platelet counts fell by 15% during hemoperfusion over coated or uncoated charcoal and also during passage through an identical empty chamber. On the other hand, with heparinized whole blood, platelet counts fell by 90% during hemoperfusion over uncoated charcoal, and 25% during hemoperfusion over coated charcoal. The concentrations of coagulation factors II, V, IX, X and XII were reduced during hemoperfusion over uncoated charcoal, while those of factors II and X were reduced and that of factor VII increased during hemoperfusion over coated charcoal. Perfusion with heparinized, platelet-rich plasma resulted in small reductions in platelet counts, suggesting that either erythrocyte disruption or the physical effects of intact red cells play a major role in producing the hemostatic abnormalities occurring during whole blood hemoperfusion. The method described may be used to assess the hemocompatibility of polymer coatings for charcoal particles, to investigate the nature of the interaction between platelets and artificial surfaces, and to assess the effect of platelet-active agents in reducing platelet adsorption on charcoal or other sorbents.     

Effect of Hemoperfusion with Coated and Uncoated Charcoal on Human Blood in Vitro

During 4 hours, in-vitro hemoperfusion of human blood was performed in 4 series of experiments: control, cellulose coated charcoal, polyacryìohydrogel coated charcoal and uncoated charcoal. In the control series little change on corpuscular elements and electrolytes was observed. In all hemoperfusion series there was little change of RBC and uniformly a marked fall of the granulocyte count. Platelet- and lymphocyte counts were significantly less affected by cellulose coated charcoal than by the other preparations. Coated and uncoated charcoal absorbed avidly calcium and glucose from the blood. By contrast the potassium level decreased moderately with polyacrylohydrogel coated and uncoated charcoal, whereas the opposite was observed with cellulose coated charcoal.     

Influence of Hemoperfusion on the Concentrations of Calcitonin, Testosterone and Cortisol in Blood Plasma

The influence of hemoperfusion with a cellulose-acetate-coated charcoal column (Adsorba 300-C, Gambro, Lund, Sweden) on plasma concentrations of calcitonin, testosterone and cortisol was studied in five psoriatic patients during 12 treatment periods. Calcitonin, testosterone and cortisol were effectively removed from blood plasma by the charcoal column with average plasma clearances of 34.0, 14.5 and 27.6 ml/min, respectively, at 30 minutes of hemoperfusion, and 4.9, 15.4 and 24.4 ml/min, respectively, at 180 minutes of hemoperfusion. After three hours of hemoperfusion, significant decreases of testosterone and cortisol were found in peripheral venous blood, while calcitonin fell insignificantly. It remains to be elucidated whether long-term use of hemoperfusion would require a detailed control of possible effects on the endocrine status of patients.     

Problems of Competition in Charcoal Hemoperfusion for the Treatment of Intoxications

Both toxic and physiological substances are adsorbed during an extracorporeal hemoperfusion for the treatment of exogenous and endogenous intoxications. Using a closed circuit in vitro, we perfused one liter saline or fresh human plasma with 4425 mumol creatinine, 4854 mumol and 97,086 mumol barbital-Na, 597 mumol bromthalein, 1942 mumol and 29,126 mumol raffinose, and 200 mumol inulin in different combinations over 70 gm of uncoated charcoal with the following results: 1. The adsorptive capacity of other substances is not influenced by preadsorption of the charcoal with a low or middle molecular weight substance; 2. In the low and middle molecular weight range, there is no competition between two substances in a solution; 3. The simultaneous usage of two substances of middle and high molecular weight, or preadsorption with a high molecular weight substance, reduces the rate of adsorption and the capacity of charcoal for middle molecular weight substances, but not for low molecular weight substances.     

Coated carbon hemoperfusion provides limited clearance of protein-bound solutes

This study assessed the capacity of a cartridge containing coated granular carbon to clear protein-bound solutes. Clearances for test solutes were measured while an albumin solution representing plasma was pumped from a 10 L reservoir through the cartridge at a rate of 200 mL/min for 5 h. Clearance values for phenol red, phenytoin, and indican were well below the limit imposed by the plasma flow and declined with time. The clearance of phenol red, which was the most tightly bound solute, fell from 38 +/- 12 to 17 +/- 2 mL/min. Additional studies revealed that the cartridge contained enough carbon to absorb all the protein-bound test solutes, but that the rate of their clearance was limited by the inability of granular carbon to take up solutes rapidly at a low concentration. The rate of solute uptake at low concentration was shown to be much greater when carbon was in powdered rather than granular form. A device in which approximately 50 g of powdered carbon was recirculated in the dialysate compartment of hollow fiber kidneys cleared phenol red and phenytoin more rapidly than the hemoperfusion cartridge containing 300 g of coated granular carbon. These results indicate that hemoperfusion over coated granular carbon provides limited clearance of protein-bound solutes.     

Digoxin Removal from a Patient with Renal Failure by Hemoperfusion with Amberlite XAD-4 Resin

A digitoxic patient with severe renal failure underwent two hemoperfusion treatments with Amberlite XAD-4 resin. Digoxin clearances calculated from plasma flow rates and plasma digoxin concentrations, as well as from the amount of digoxin eluted from the used columns, were superior to those previously described for peritoneal dialysis, hemodialysis and charcoal hemoperfusion. There was a temporary improvement in the patient's life-threatening digitoxic cardiac rhythm with the first hemoperfusion, and a permanent improvement after the second hemoperfusion. It is submitted that hemoperfusion with this resin may significantly lessen manifestations of digoxin poisoning and may hasten digoxin elimination in digitoxic patients with renal failure.     

Comparison of a Charcoal Sorbent Fiber with Commercial Charcoals for Hemoperfusion

A charcoal sorbent fiber (Enka, F.R.G.), was assessed for impurities, surface area, and adsorptive properties of its native charcoal, and compared with other uncoated activated charcoals. In vivo and in vitro hemocompatibility of the fiber were assessed as well as the adsorptive properties for endogenous toxins. The charcoal of the fiber had few impurities and a high surface area of 1,200 m2/g charcoal. For measuring the adsorptive speeds, 2 g of the uncoated charcoals were milled and screened to a particle size of 150-250 microns (Enka; 30-40 microns) and then mixed with the solutions of the individual solutes. The charcoal types of Enka, used in the charcoal sorbent fiber, and of Sutcliffe Speakman, used in the acrylic hydrogel coated charcoal, exhibited the highest adsorptive rates for bromthalein (middle molecular weight marker) and inulin (high molecular weight marker). No hematological differences among the various charcoals were found during the in vivo hemoperfusions. In the in vitro hemoperfusions with heparinized fresh blood, the fibers showed the lowest loss of leucocytes and thrombocytes. In the in vitro evaluation of the absorbents for hepatic support, the charcoal fiber and the petroleum pitch charcoal of Asahi had the best adsorptive properties for substances in the low molecular weight range.     

Sustained Low-Efficiency Daily Diafiltration with Hemoperfusion as a Therapy for Severe Star Fruit Intoxication: A Report of Two Cases

Abstract

Over the past decade, star fruit (Averrhoa carambola) intoxication decreased in the Taiwanese society due to improved public education on chronic kidney disease (CKD). Various complications including hiccups, altered levels of consciousness, coma, and seizures have been reported in individuals with renal failure who ingested fresh star fruit or star fruit juice. A high mortality rate (from 33 to 80%) was observed in patients with altered levels of consciousness, despite prompt dialysis and supportive care. According to previous case reports, the proposed treatment of choice for severe star fruit intoxication may be continuous renal replacement therapy with or without hemoperfusion. We report two cases of star fruit intoxication with stage V CKD (one case is predialysis) presenting with coma and generalized tonic-clonic seizures. The two patients were treated with sustained low-efficiency daily diafiltration (SLEDD-f) and charcoal hemoperfusion. Status epilepticus was controlled fairly quickly after treatment with SLEDD-f and hemoperfusion. However, the outcomes in this report are still poor (both remained comatose; one of two patients died). Currently, there are no data for the use of SLEDD-f with hemoperfusion for severe star fruit intoxication. SLEDD-f with charcoal hemoperfusion may play a role in managing refractory status epilepticus in patients with severe star fruit poisoning.     

Present and Future Uses of Hemoperfusion with Sorbents

International interest in the clinical uses of hemoperfusion has increasingly grown in the last ten years and, as a result, sorbent hemoperfusion has emerged as first-line management in several areas. This center and many others have shown that there is a clear role for hemoperfusion in severe self-poisoning. Plasma extraction ratios for most drugs are significantly higher for hemoperfusion over both resin (0.8) and activated charcoal (0.5; CHP) than for hemodialysis (0.27), under similar conditions of blood flow, plasma drug concentrations, etc. Using appropriate pharmacokinetic models in the analysis of plasma drug profiles, it has been shown that CHP can increase drug elimination rate constants and whole body clearance rates in experimentally intoxicated animals. Enhancement of drug elimination broadens the scope of sorbent hemoperfusion to other areas of application, such as the removal of anticancer drugs (e.g., methotrexate, adriamycin) after cancer chemotherapy. Evaluation of the role of hemoperfusion in hepatic encephalopathy or uremia is limited by the lack of knowledge regarding specific toxic molecules in these syndromes. Nevertheless, in the authors' series of ten patients with fulminant hepatic failure, four survived, in contradistinction to an 80–90% mortality for untreated patients, and virtually all awoke from deep coma. Accompanying reversal of coma, there were significant changes in plasma and cerebrospinal fluid amino acids and in cerebrospinal fluid cyclic AMP concentrations. This suggests that hemoperfusion over charcoal in hepatic encephalopathy may be a useful technique. In this series of uremic patients, although hemoperfusion with charcoal has been shown capable of adsorbing putative uremic toxins including middle molecules up to the present, hemoperfusion alone is only marginally superior to standard hemodialysis. Fouremia, it is likely that multiple specific sorbents will be required, and several compounds for urea and creatinine sorption are presently under investigation.     

Liver Support Systems: A 1978 Perspective

The present status of support systems and devices for the injured liver is reviewed with emphasis on both long-term and short-term substitution. Long-term replacement can only be possible by the grafting or transplantation of a human and/or other primate liver. Most artificial systems may be applied for short-term biological and technical substitution, e.g., by hemodialysis/hemoperfusion through adsorbents and resins. More sophisticated devices for detoxification of blood or cell-free plasma in acute liver failure should combine the catalytic specificity of immobilized microsomal enzymes with the adsorptive capacity of activated charcoal, resins and affinity gels.     

Aluminium release by coated and uncoated fluid-warming devices

The use of fluid-warming systems is recommended for infusion rates > 500 ml.h⁻¹ to avoid peri-operative hypothermia. Some fluid-warming devices use disposable aluminium-heated plates for heat transfer, but there is no protective coating to separate the fluid from the heated aluminium surface. It is unknown if this could promote release of aluminium into infusion fluids. We investigated a coated (Fluido compact) and an uncoated (enFlow) fluid-warming device using normal saline or balanced electrolyte solution as infusion fluids, pumped through the heated disposables at flow rates of 2, 4 and 8 ml.min⁻¹ for 60 min each. Aluminium concentrations in the fluid samples were analysed using graphite furnace atomic absorption spectrometry. With saline the coated and uncoated devices yielded aluminium concentrations below the level of quantification (< 128 μg.l⁻¹). Similarly, balanced electrolyte solution in the coated device yielded aluminium concentrations < 128 μg.l⁻¹. However, balanced electrolyte solution in the uncoated device yielded aluminium concentrations of up to 6794 (3465–8002 [1868–7421]) μg.l⁻¹. Repeating this last study at a flow rate of 2 ml.min⁻¹ resulted in quite high aluminium concentrations when the uncoated device was not heated (~1000 μg.l⁻¹) and higher concentrations after the device was heated. We conclude that using uncoated aluminium plates in fluid-warming systems can lead to a risk of administering potentially harmful concentrations of aluminium when balanced crystalloid solutions are used. The mechanism is unclear, but heat is in part involved. Coating for aluminium within medical devices in direct contact with infusion fluids should be recommended.     

Hemoperfusion versus Hemodialysis in the Management of Patients Severely Poisoned by Organophosphorus Insecticides and Bipyridyl Herbicides

Organophosphorus insecticides (parathion, demeton-S-methyl sulfoxide, dimethoate) inhibit cholinesterase activity. Besides the well-known resulting biochemical changes, there is evidence of direct toxic effects due to an excess of organophosphorus in blood and tissue. The therapeutic measure described here aims at eliminating organophosphorus. Hemodialysis (HD) has no effect in parathion poisoning, but hemoperfusion with coated activated charcoal (HP-CHAR) results in a clearance of 59.20% of the blood flow (ml/min) while the HP clearance with Amberlite XAD-4 (HP-XAD) is 81.33%. HD may be used in poisoning by demeton-S-methyl sulfoxide (clearance: 52.98%), and dimethoate (clearance: 59.07%), but HP-CHAR clearance is much higher (83.70% and 87.84%, respectively). HP-XAD clearance even reaches 100% of the blood flow. Demeton-S-methyl sulfoxide and dimethoate are distributed almost equally in blood and tissue, and the effect of HP is indicated by a rapid decline in blood organophosphorus level as well as by an improvement in the signs and symptoms of the patient. Parathion accumulation is six to eight times higher in the tissue. This means there is protracted decline in blood level because of redistribution and less clinical evidence of improvement. However, animal trials demonstrate that HP-CHAR results in a significantly faster decrease in parathion concentration in muscle and brain as compared with the control group. Hence, HP is an effective method for removing toxicologically relevant amounts of organophosphorus from the body. Oral poisoning with bipyridyl herbicides such as paraquat (Gramoxone®) and diquat (Reglone®) is extremely serious. Fatal consequences occur after even one to three mouthfuls of the commercial liquid preparations. The literature reports that patients whose plasma levels within the first 48 hours exceed 0.1-0.2 μg/ml have died, regardless of therapy. Recently, two patients with severe suicidal poisonings were treated by almost continuous HP (and HD) using 12 and 21 columns, respectively, for a period of two to three weeks. Paraquat plasma levels were 1.12 μg/ml and 1.44 μg/ml, respectively, within the first 48 hours after ingestion. Both patients survived without lung damage. HP-CHAR clearance (72.7 ml/min, blood flow 100 ml/min) clearly exceeds that of HD (11.5 ml/min, blood flow 100 ml/min) at these blood levels. Probably the affinity of coated activated charcoal for paraquat is superior to that of lung tissue. Hence, continuous HP-CHAR is recommended in severe paraquat poisoning.     

Nonporous silicone polymer coating of expanded polytetrafluoroethylene grafts reduces graft neointimal hyperplasia in dog and baboon models

Purpose: Neointimal hyperplasia frequently develops after placement of prosthetic vascular grafts and is a major cause of graft failure. This study was an attempt to prevent vascular lesion formation by coating the graft luminal surface with a thin layer of nonporous silicone polymer, and subsequently with an ultrathin layer of vapor phase (plasma gas) deposited fluoropolymer, thereby providing a smooth and chemically uniform surface that was postulated to limit pannus tissue ingrowth across the graft anastomoses.Methods: Bilateral femoral arteriovenous (AV) conduits were constructed in four dogs using expanded polytetrafluoroethylene graft materials (ePTFE; 6-mm inside diameter, 2.5-cm long). In each animal, one femoral AV shunt was constructed from a graft whose luminal surface was entirely coated with polymer. On the contralateral side, an uncoated graft served as a control. Bilateral aortoiliac grafts were placed in three baboons using 5-cm segments of ePTFE (4-mm inside diameter). One end (1 cm) of each graft had been coated with polymer. In each animal, the coated end of one graft was placed proximally and the coated end of the second graft was placed distally in the contralateral vessels.Results: All grafts were patent at 30 days. In the dog model, there was a significant reduction in graft neointimal area at the venous anastomoses for the coated grafts compared with the uncoated grafts (0.03 ± 0.02 mm ² and 1.11 ± 0.54 mm ² , respectively; p < 0.05). In the baboon model, the silicone coating significantly reduced the graft neointimal thickness (0.003 ± 0.003 mm vs 0.21 ± 0.05 mm; p < 0.05) and neointimal area (0.05 ± 0.08 mm ² vs 0.82 ± 0.58 mm ² ; p < 0.05).Conclusions: These data demonstrate that healing of ePTFE grafts can be effectively modified by altering the physical properties of the graft surface. Neointimal hyperplasia within ePTFE grafts is significantly reduced by the local application of a fluorocarbon-coated, silicone-based polymer. The resulting graft flow surface effectively prevents tissue ingrowth from the adjacent native vessel, thereby preserving the anastomosis luminal area. This approach could represent a new strategy for limiting graft surface anastomotic neointimal hyperplasia. (J Vasc Surg 1996;24:825-33.)     

Coating Membranes for a Sorbent-Based Artificial Liver: Adsorption Characteristics

Techniques are described for the coating of sorbents to be used in an artificial liver support system based on mixed sor-bent bed hemoperfusion. Activated charcoal has been coated with cellulose acetate (CA) by solvent evaporation. With Amberlite XAD-4, the Wurster technique was used for coating with CA. XAD-4 has also been coated with a synthetic poly-electrolyte with anticoagulant activity by adsorption and fixation by gamma radiation-induced crosslinking. Activated charcoal, XAD-4, and a cation exchange resin, all in powdered form, were encapsulated in agarose gel beads. Adsorption characteristics onto the sorbents are described. The results are in agreement with a theoretical model presented. In general, adsorption onto XAD-4 is limited by film diffusion. With activated charcoal, pore diffusion limitation is generally observed. Blood compatibility is improved by coating.     

Silikatisierte/silanisierte Implantatoberflächen zur optimierten hydrolysestabilen Verbundfestigkeit zwischen Knochenzement und Metall

Background

The aseptic loosening of cemented total hip and knee arthroplasties is still an unsolved problem. In this regard, the hydrolytic resistance in the metal-to-bone cement interface is of major importance.

Methods

Cemented pretreated femur stems and tibia components coated by means of a silica/silane interlayer system were dynamically loaded with the help of a hip and knee simulator similar to DIN ISO Norm. After loading, the components were microscopically analysed concerning both debonding in the metal-to-bone cement interface and cement mantle defects. These data were matched with uncoated components. Unloaded coated and uncoated femur and tibia components acted as controls.

Results

Compared with uncoated components, the pretreated and coated ones yielded a significant reduction in cement defects as well as of debonding in the metal-to-bone cement interface.

Conclusion

Using the silica/silane interlayer system for cemented femur and tibia components, hydrolytic debonding in the metal-to-bone cement interface with following cement mantle failure can be reduced. This could help increase the long-term stability of the metal-to-bone cement compound, with decreased aseptic loosening.     

Haemodiafiltration with sorbent-regenerated ultrafiltrate as replacement fluid: a multicenter study

BACKGROUND: Uncoated adsorbent charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The objective of this study was to assess the safety and the long-term clinical results. METHODS: Thirty-three chronic uraemic patients were dialysed for 1 year using two haemodialysers in series in order to separate convection from diffusion. At the outflow of the convective haemofilter, a cartridge containing 130 g of uncoated charcoal was inserted. The regenerated ultrafiltrate was then infused at the entrance of the diffusive dialyser. Ex vivo and in vitro studies were performed to analyse the adsorption characteristics and the release of aluminium, other trace elements, and microparticles. RESULTS: Passage through the charcoal left urea, phosphate, potassium, calcium, and bicarbonate concentrations unchanged. Creatinine, uric acid and beta 2- microglobulin were almost completely absorbed by the charcoal. Aluminium release was dependent upon time of storage, as inferred from studies on inter-lot variability. Washing with bicarbonate buffer (pH 7.0) allowed reduction of aluminium levels to within the pharmacopoeia requirements for intravenous fluids. No significant pre- or post- charcoal differences were observed for several trace elements such as manganese, selenium, arsenic, cadmium, mercury, lead, chromium and zinc. Copper was completely retained in the charcoal. Regenerated ultrafiltrate infused at the entrance of the diffusive dialyser was free of microparticles, bacteria, and endotoxin. Clinical tolerance was excellent and blood pressure control satisfactory. A significant decrease in serum values of beta 2-microglobulin was observed at 6 and 12 months of treatment. CONCLUSIONS: Reinfusion of ultrafiltrate through an uncoated charcoal cartridge proved to be a safe, well- tolerated and simple technique. Further potential benefits of regenerated ultrafiltrate may also include the maintenance of acid-base balance with reinfusion of endogenous bicarbonate.      

Prominent Accumulation in Hemodialysis Patients of Solutes Normally Cleared by Tubular Secretion

Dialytic clearance of urea is efficient, but other small solutes normally secreted by the kidney may be cleared less efficiently. This study tested whether the high concentrations of these solutes in hemodialysis patients reflect a failure of passive diffusion methods to duplicate the efficacy of clearance by tubular secretion. We compared the plasma concentrations and clearance rates of four solutes normally cleared by tubular secretion with the plasma concentrations and clearance rates of urea and creatinine in patients receiving maintenance hemodialysis and normal subjects. The predialysis concentrations (relative to normal subjects) of unbound phenylacetylglutamine (122-fold), hippurate (108-fold), indoxyl sulfate (116-fold), and p-cresol sulfate (41-fold) were much greater than the concentrations of urea (5-fold) and creatinine (13-fold). The dialytic clearance rates (relative to normal subjects) of unbound phenylacetylglutamine (0.37-fold), hippurate (0.16-fold), indoxyl sulfate (0.21-fold), and p-cresol sulfate (0.39-fold) were much lower than the rates of urea (4.2-fold) and creatinine (1.3-fold). Mathematical modeling showed that prominent accumulation of the normally secreted solutes in hemodialysis patients could be accounted for by lower dialytic clearance relative to physiologic clearance combined with the intermittency of treatment. Whether or not more efficient removal of normally secreted solutes improves outcomes in dialysis patients remains to be tested.Hemodialysis is now prescribed to provide a standard fractional reduction in the plasma urea concentration. The adoption of urea as our index solute has had the unintended consequence of maximizing the apparent efficacy of treatment. The dialytic clearance of urea is high, because it diffuses rapidly from both red cells and plasma. The native kidney clearance of urea, by contrast, is lower than the clearance of many solutes because of tubular reabsorption. As a result, conventional three times per week hemodialysis provides a time-averaged urea clearance, which is about one fourth of the clearance provided by the native kidneys. The efficacy of dialysis is reduced by intermittency, but predialysis plasma urea concentrations are still maintained within five to ten times the normal value.¹Recent reports have emphasized, however, that hemodialysis can be much less effective in controlling the levels of other small solutes.^2–5 Pretreatment levels of individual solutes have been reported to rise as high as 100 times the normal value. The current study examined why conventional treatment leaves the concentrations of some solutes so high. Mathematical modeling predicted that dialysis, which clears solutes by diffusion, would be relatively ineffective in controlling the levels of solutes that the native kidney clears efficiently by secretion. This prediction was tested by measuring the plasma concentrations and clearance rates of four solutes normally cleared largely by secretion—phenylacetylglutamine, hippurate, indoxyl sulfate, and p-cresol sulfate—and comparing them with the concentrations and clearance rates of urea and creatinine. The dialytic clearances of the normally secreted solutes were low relative to their native kidney clearances. In accordance with the prediction of the model, conventional hemodialysis was relatively ineffective in controlling the levels of these solutes. Additional analysis showed that hemodialysis is particularly ineffective in controlling solute levels when a low dialytic-to-native kidney clearance ratio is combined with a high fractional reduction in the solute concentration during intermittent treatment.     

Hyaluronan based heparin free coated open and closed extracorporeal circuits for high risk coronary revascularization

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were prospectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n = 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n = 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n = 12); and Group 4: Control-open, uncoated ECC (n = 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p < .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p < .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed + coated group at T4 (p < .05). Postoperative hemorrhage (mL) was 510 +/- 40 in closed + coated and 536 +/- 40 in open + coated groups (control: 784 +/- 48, p < .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 +/- .01 in closed+coated, 2.01 +/- .01 in open+coated, and 3.3 +/- .015 in control groups (p < or = .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.     

Analysis of Hydroxyapatite Surface Coverage by Amelogenin Nanospheres Following the Langmuir Model for Protein Adsorption

The assembly of amelogenin protein into nanospheres is postulated to be a key factor in the stability of enamel extracellular matrix framework, which provides the scaffolding for the initial enamel apatite crystals to nucleate and grow. Adsorption isotherms were evaluated in order to investigate the nature of interactions of amelogenin nanospheres with hydroxyapaite crystals in solution, where their assembly status and particle size distribution are defined. We report that the adsorption isotherm of a recombinant mouse amelogenin (rM179) on synthetic hydroxyapatite crystals can be described using a Langmuir model indicating that amelogenin nanospheres adsorb onto the surface of apatite crystals as binding units with defined adsorption sites. The adsorption affinity and the maximum adsorption sites were 19.7 × 10⁵ L/mol and 6.09 × 10^–7 mol/m², respectively, with an r² value of 0.99. Knowing the composition and particle size distribution of amelogenin nanospheres under the condition of adsorption experiments, we have calculated the number of nanospheres and the crystal surface area covered by each population of nanospheres at their maximum adsorption. It was found that total maximum binding covers 64% of the area unit. This observation supports the speculation that amelogenin binding onto apatite surface is selective and occurs only at certain sites. Present address for N.B.: Department of Material Science, University of Patras, GR-26500 Patras, Greece     

The Thin-Film Adsorber Hemoperfusion Device: Development and Evaluation of Clearance Characteristics

A novel hemoperfusion device was developed by embedding powered activated charcoal in thin (150 μm) films of cellulose nitrate. These films were sprinkled with small particles of granular charcoal and wound into spools, which were then placed in a plastic housing. The use of powdered charcoal exploits the enormous rate-of-uptake advantage of powered charcoal over the granular sorbents found in other hemoperfusion devices. The granular carbon sprinkled on the films was primarily to provide spacing between adjacent film layers for adequate fluid flow; the granules did enhance long-term uptake in addition. Clearance tests with this novel "thin-film adsorber," using sodium salicylate, sodium barbital, and creatinine, showed that its rate of solute adsorption, particularly at early times, was consistently very high. This type of hemoperfusion device is a promising alternative to the granular-sorbent types of devices currently available, especially when maximal solute removal during the early stages of treatment is mandated.