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PubMed1987

Relation between complement activation and susceptibility to decompression sickness.

The consequences of complement activation and the symptoms of decompression sickness are similar. Consequently, the relation between the sensitivity of individuals to complement activation by air bubbles and their susceptibility to decompression sickness has been examined. Plasma samples from 34 individuals were incubated with air bubbles, and the concentration of the fluid phase metabolites of complement activation C3a, C4a, and C5a were measured with radioimmunoassays. It was found that both the anaphylatoxins C3a and C5a were produced by the presence of air bubbles but that the anaphylatoxin C4a was not. This finding indicates that air bubbles activate the complement system by the alternate pathway. One group of individuals was found to be particularly sensitive to complement activation by this pathway. They produced 3.3 times more C3a and 5.3 times more C5a in their plasma samples incubated with air bubbles as did the other group. Sixteen individuals were subjected to a series of pressure profiles that were severe enough to produce bubbles in their circulatory system that could be detected by Doppler ultrasonic monitoring. The group of individuals that had been identified as being more sensitive to complement activation by the alternate pathway was also found to be more susceptible to decompression sickness.

Adult↗
PubMed1986

Density changes in leukocytes following hemodialysis or exposure to chemotactic factors.

Analysis of standard Ficoll-Hypaque separation profiles of peripheral WBC from patients undergoing hemodialysis (HD) demonstrated that dialysis caused a marked alteration in the number of cells found at both the interface between the Ficoll-Hypaque and plasma which normally contains mononuclear cells and the cell pellet which normally contains granulocytes. By 30 min into dialysis, there was a 175% increase in white blood cells in the mononuclear band with a corresponding decrease in the number of cells obtained from the cell pellet. When peripheral blood samples from normal donors were pumped through various types of hemodialyzers, a shift in the cell separation profiles similar to that of patients undergoing HD was observed. Differential analysis of the cells obtained from both the interface between the Ficoll-Hypaque and plasma and the cell pellet showed that by 30 min into dialysis, the 'mononuclear' band contained 40-50% polymorphonuclear neutrophils (PMN). To ascertain whether the cell separation changes were possibly due to C5a generation resulting from complement activation by the HD membrane, whole blood was incubated with the purified chemotactic factors C5a, C5ades arg, and formyl-methionyl-leucyl-phenylalanine. This resulted in similar alterations in PMN densities. This study demonstrates that both in vivo and in vitro exposure of human peripheral blood to HD membranes as well as the chemotactic factors C5a, C5ades arg, and formyl-methionyl-leucyl-phenylalanine results in density changes in PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Anaphylatoxin C5a generation and dialysis-induced leukopenia with different hemodialyzer membranes.

Leukocyte counts and plasma C5a anaphylatoxin levels were studied during hemodialysis in patients using Cuprophan, polycarbonate and polyacrylonitrile membrane dialyzers. Cuprophan induced a marked leukopenia with significant plasma C5a generation. Polycarbonate promoted the same trend of changes in both parameters but significantly less pronounced, while polyacrylonitrile did not affect leukocyte counts nor plasma C5a levels. These data suggest that complement-derived C5a generation may be an important factor in the mechanism of hemodialysis-induced leukopenia.

Acrylic Resins↗
PubMed1986

Biocompatibility of a new polycarbonate dialysis membrane.

The present report summarizes our experience with a new polycarbonate (PC)-based dialysis membrane (Gambro Lundia PRO-5) compared with a cuprophan (CP)-based membrane (Gambro Lundia 10-5N). Platelet count decreased during dialysis with CP, but was unchanged with PC membranes. Platelet injury, reflected by decreased platelet aggregation and increase in plasma beta-thromboglobulin, occurred equally with both membranes. Complement activation (C3d and C5a), leukopenia and release of granulocyte-derived elastase was more extensive with CP than with PC membranes. The new membrane represents an improvement of biocompatibility with respect to the complement-leukocyte system, whereas the effect on platelets resembles the injury caused by CP membranes.

Adenosine Diphosphate↗
PubMed1986

Performance and biocompatibility of a new hemodialysis membrane.

Performance studies and investigations of the biocompatibility of a new hemodialysis membrane were conducted in patients being chronically hemodialyzed. The investigated polycarbonate membrane revealed a very satisfying performance with regard to clearance values and the ultrafiltration rate. The biocompatibility studies showed a significant leukopenia and an increase of C5a, platelet factor 4 and granulocyte elastase. Thrombocytes and C3d remained unchanged. Long-term studies have to confirm whether or not the new membrane is more biocompatible, a suggestion which could be advanced, as no febrile episodes were observed during any treatment, a finding which is not typical for Cuprophan hemodialysis.

Biocompatible Materials↗
PubMed1987

Biocompatibility of artificial organs: an overview.

Papers that are presented in this symposium on biocompatibility of foreign surfaces used in artificial organs are commented upon and set in an overall context of the biocompatibility of foreign surfaces to blood. A working formulation of the events comprising lack of biocompatibility of hemodialysis membranes to the complement system is given as a possible model to which other foreign surfaces may be compared.

Animals↗
PubMed1987

Biocompatibility of different hemodialysis and plasmapheresis membranes.

The biocompatibility of different membranes was assessed by measuring changes in different white blood cell counts, PGE2 concentrations, thromboplastin activity, production of anaphylatoxins and clinical parameters during treatment. The in vivo recorded complement activation was compared with in vitro experiments. Hemodialysis (HD) treatment was performed with 5 different membranes. Plasmapheresis was run with cellulose diacetate membranes in single (SMF) and double (DMF) membrane filtration and with a new polycarbonate membrane in SMF. The polysulfone membrane was found to be the most, and the cuprophane membrane the least biocompatible membrane in HD. However, large individual differences from one HD patient to the other were found. In contrast to the cellulose diacetate membrane, the polycarbonate membrane apparently activated no complement along the blood-membrane interface during plasmapheresis, but activated large amounts within the membrane matrix. High blood concentrations of C5a were promptly cleared in the body, while high concentrations of C3a seemed to block the removal of this substance from the blood compartment. Even when the patients had high blood concentrations of anaphylatoxins throughout the plasmapheresis treatments using cellulose diacetate membranes and when a significant activation of PGE2 was found in patient plasma, no activation of thromboplastin was recorded on the surface circulating monocytes.

Biocompatible Materials↗
PubMed1987

Analysis of density changes and chemotactic receptors of leukocytes from chronic hemodialysis and peritoneal dialysis patients.

Analysis of standard Ficoll-Hypaque (density = 1.077 g/ml) separation profiles of peripheral white blood cells (WBC) from patients undergoing hemodialysis (HD) demonstrated that dialysis caused a marked decrease in the density of polymorphonuclear leukocytes (PMN) resulting in about 50% of these cells separating with the mononuclear cells. In vitro exposure of normal control peripheral blood to HD membranes as well as to the purified chemotactic factors C5a, C5ades-Arg, and formyl-Met-Leu-Phe (fMLP) also resulted in PMN density changes which altered the Ficoll-Hypaque separation profiles of WBC. Therefore, these results imply that C5a generation, resulting from complement activation by the HD membrane, induced the density changes in the PMN from HD patients. Further studies using flow cytometry and fluorescein-labeled chemotactic factors (C5a, formyl-Met-Leu-Phe-Lys [fMLPL] and casein) indicated that HD patients had a significant reduction in the ability of their PMN and monocytes to bind C5a. This contrasted with the findings of no significant difference in the percentage or fluorescence intensity of HD patients' PMN or monocytes binding casein or fMLPL. Functional studies to analyze chemotactic-factor-mediated responses indicated that there was a decreased ability of HD patients' PMN and monocytes to generate superoxide anion, produce H2O2 and release myeloperoxidase in response to both C5a and fMLP. Additional studies evaluated the binding of chemotactic factors to PMN and monocytes from normal blood following passage through a hemodialyzer and from patients undergoing HD. Analysis of receptor binding by control cells passed through the dialyzer showed that there was a progressive decrease in the percentage of C5a-receptor-positive PMN and monocytes but no change with casein or fMLPL. In contrast, peripheral PMN and monocytes from chronic renal failure patients on HD showed no difference in C5a, casein or fMLPL receptors during the course of HD as compared to the predialysis period. This appears to be attributable to a difference in the regulation of the C5a that is generated as a result of the dialysis-membrane-induced activation of the complement system. Although C5a has been shown to be continuously generated during the course of HD, these patients show no modulation of their C5a receptors during the course of HD or when their whole blood is exposed to dialysis membrane fibers. These findings suggest that there are mechanisms functioning in chronically dialyzed patients to protect them from the effects of excessive C5a generation during HD.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Separation↗
PubMed1987

Assessment of complement activation during extracorporeal circulation by measurement of complement split C3d.

The present report summarizes our previous experience with the effect of various dialyzer membranes on leukocyte count, plasma C3d and C5a/C5ades-Arg, and total hemolytic complement. A relationship between the formation of C5a/C5ades-Arg within the dialyzer and hemodialysis leukopenia was demonstrated by comparing different membranes. Arterial plasma C3d was found to be a useful cumulative marker of complement activation during hemodialysis. C3d was shown to be generated in the artificial kidney with kinetics resembling the formation of C5a/C5ades-Arg. Total hemolytic complement transitorily decreased with all membranes, but did not reflect dialyzer biocompatibility. It is suggested that determination of complement-split C3d outdates previous more elaborate estimates of complement activation during hemodialysis.

Complement Activation↗
PubMed1987

Analysis of membrane processes for blood purification.

Physical phenomena play an important role in membrane processes for blood purification. They largely determine the separation performance of these devices and they interact with chemical and biological phenomena to determine their biocompatibility, or lack thereof, in the clinical setting. In the first part of this paper, analyses of physical phenomena which determine the separation and purification characteristics are reviewed for several processes, including hemodialysis, hemofiltration, combined hemodialysis and ultrafiltration, and membrane plasmapheresis with cross-flow microfiltration. Special attention is given to transport of high-molecular weight solutes in hemodialysis, for use in subsequent analyses, and to the factors which determine filtrate flux in membrane plasmapheresis, because recent findings in this area provide an understanding of filtration processes in general. The second part concerns the problem of biocompatibility, especially as manifested in renal prostheses. After reviewing some of the pathways to bioincompatibility, exploratory analyses are presented using relatively simple models. The objective of these analyses is to provide an initial quantitative framework for examining the likelihood of monocyte secretion of interleukin-1 being stimulated by various routes. Issues examined, for which illustrative calculations are presented, include (1) transport of endotoxin fragments across regenerated cellulose and other membranes, (2) anaphylatoxin C5a concentrations in conventional hemodialysis and (3) the effects of equilibrium and reaction phenomena, ultrafiltration, diffusive membrane permeation and membrane adsorption on the disposition of C5a which is generated at the membrane surface.

Animals↗
PubMed1988

Good biocompatibility of the polyamide hemofilter.

Chronic hemofiltration (HF) is now a well-established method, especially for elderly uremic patients and those suffering from cardiovascular problems. This is due to the fact that chronic HF offers superior treatment comfort with less hypotensive episodes, vomiting, muscle cramps and febrile reactions. Apart from the different blood purification techniques involved in chronic HF compared to hemodialysis (i.e. convection versus diffusion), it might well be that the better treatment comfort is attributable to a certain extent to the polyamide HF membrane used in our HF treatments. We studied different biocompatibility parameters and received the following data: (a) leukocytes and thrombocytes remained unchanged during a treatment session; (b) elastase increased slightly but there was no difference between the polyamide and polycarbonate membrane, and (c) arterial and venous concentrations of C5a and C3d remained almost unchanged. The superior treatment comfort and better vascular stability of HF over hemodialysis might also be due to the improved biocompatibility of the applied hemofilter as the polyamide membrane induces no changes in different biocompatibility parameters such as leukocytes, thrombocytes, C5a or C3d.

Biocompatible Materials↗
PubMed1988

Generation and removal of anaphylatoxins during hemofiltration with five different membranes.

The generation of anaphylatoxins (C3a and C5a) during hemofiltration with polysulfone (F60), acrylonitrile (AN69 HF), polyamid (FH77), polyacrylonitrile (PAN200) and cellulose-acetate (Duo-Flux) membranes were investigated. The 'net' production of C3a in the blood compartment during the treatment was 3,028 micrograms (Duo-Flux), 1,845 micrograms (FH77), 270 micrograms (F60), -2,388 micrograms (AN69 HF) and -5,189 micrograms (PAN200), the latter two negative values reflecting a high adsorption of C3a to the membrane material. Corresponding values for C5a were 185 micrograms (AN69 HF), 108 micrograms (F60), 83 micrograms (PAN200), 6 micrograms (FH77) and -133 micrograms (Duo-Flux). The sieving coefficient remained stable for C5a throughout the treatment, while it fell significantly for C3a with the F60 membrane (0.44-0.25) and increased significantly for the FH77 membrane (0.14-0.33). The cellulose-acetate membrane device produced the most pronounced drop in white blood cell counts and the acrylonitrile membrane the least. The Duo-Flux device was significantly less biocompatible than the other membranes investigated, while little differences were found between AN69 HF, F60, FH77 and PAN200. When hemodialysis is compared with hemofiltration employing the same membranes, the latter appears to be a more biocompatible treatment modality partly due to convective removal of activated complement from the blood compartment into the filtrate.

Anaphylatoxins↗
PubMed1986

Serum profiles of the regulatory complement proteins during the progression of renal damage in human glomerulonephritis.

Persistent activation of the complement system after escape from control by the regulatory proteins results in an excessive release of split products with inflammatory properties. Serum levels of the regulatory proteins of the complement system (Cl-INH, H, I and AT III) were assayed by the radial immunodiffusion technique in 521 serum samples from 124 patients with idiopathic chronic glomerulonephritis divided into two groups: 81 cases with normal renal function (NRF), and 43 cases with deteriorated renal function (DRF). Significant high mean levels of Cl-INH, H, I and AT III were found in patients with NRF, when they were compared with DRF patient groups. Positive correlations between the regulatory proteins and the corresponding complement components were found in patients with NRF, whereas they were reduced considerably in patients with DRF. Serial measurement of the control proteins showed a decay of the levels of Cl-INH, H and I in patients with progressive impairment of renal function. The presence of high levels of regulatory proteins suggest that a control mechanism may occur in patients with NRF; measurement of these proteins could, therefore, be of prognostic value, as the presence of high levels are indicative of a block of the complement system.

Antithrombin III↗
PubMed1989

Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay.

Using a specific and sensitive ELISA for C5a, the present study shows that predialysis levels of C5a in end-stage renal disease patients are not elevated and that all membranes studied (Cuprophan, Hemophan, Gambrane and hydrophilic polysulfone) cause significant increases of C5a plasma levels albeit to different degrees. Higher increases of C5a were accompanied by larger decreases of circulating granulocytes and monocytes. Dialyzers with a newly introduced modified regenerated cellulose membrane, Hemophan, showed lower C5a plasma levels during hemodialysis than Cuprophan. With Hemophan C5a plasma levels were comparable to those with polysulfone membranes.

Adult↗
PubMed1975

Effects of anesthesia, surgery and inflammation upon host defense mechanisms. I. Effects upon the complement system.

Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groupds. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the 'reactor state', a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

Anesthesia, General↗