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PubMed1999

Parafoveal arteriolar obstruction after ocular trauma in a patient with systemic lupus erithematosus.

BACKGROUND: Retinal arterial obstruction after ocular trauma is a rarely described entity which presents a still controversial pathogenesis. However, intravascular leucoembolization in response to activation of complement factor 5 (C5a) has now been hypothesized as a possible cause of arterial embolization after severe trauma. Coincidentally, the pathogenesis of vascular lesions seen in active systemic lupus erithematosus is also related to the activation of the same complement factor. METHODS: We present the case of a 32-year-old man with active systemic lupus erithematosus who received a blunt trauma in his right eye and immediate developed severe visual loss. RESULTS: Ophthalmoscopy of the affected eye revealed a cherry-red spot macula, small hemorrhages and edema of the posterior pole. Fluorescein-angiography showed obstructions and staining of small branches of arterioles in the parafoveal region. After 2 months of follow-up, the ophthalmoscopic picture evolved to optic atrophy and the visual acuity remained severely reduced. CONCLUSION: We hypothesize that patients with complement-mediated diseases are predisposed to retinal arteriolar obstruction after ocular trauma.

Adult↗
PubMed1988

Complement and leukocytes during cardiopulmonary bypass: effects on plasma C3d and C5a, leukocyte count, release of granulocyte elastase and granulocyte chemotaxis.

In an effort to further elucidate the complex changes in the complement-leukocyte system during cardiopulmonary bypass (CPB), plasma levels of C3d, C5a, and granulocyte elastase bound to alpha1-proteinase inhibitor (E-alpha1 PI) were followed prior to, during, and after CPB. Leukocyte and differential cell counts and granulocyte migration were also determined. Complement activation was documented during CPB by an increase in plasma C3d corrected for hemodilution. Significant amounts of C5a were not revealed. Cell counts decreased during CPB but, if corrected for hemodilution, remained unchanged apart from a slight decrease in lymphocyte count after 60 minutes. Eighteen hours after CPB, neutrocytosis and lymphopenia occurred. Plasma E-alpha1 PI increased during CPB, reflecting release of granulocyte lysosomal enzymes. Granulocyte migration was transitorily depressed during CPB, and it was shown that this was due to the appearance of an intrinsic cellular defect. CPB is associated with acute changes in cells and plasma, resembling an acute whole-body inflammatory response, with transitory impairment of granulocyte migration. The clinical significance of these observations remains to be determined.

Aged↗
PubMed1995

Terminal complement pathway activation and low lysis inhibitors in rheumatoid arthritis synovial fluid.

OBJECTIVE: To investigate terminal complement activation and lysis inhibitors in rheumatoid arthritis (RA). METHODS: C5a, vitronectin and clusterin were quantitated by enzyme immunoassays in plasma and synovial fluid (SF) in RA (n = 30) and osteoarthritis (OA) (n = 11). RESULTS: In RA the concentration of C5a was 3-fold increased in plasma (21.9 vs 7.2 micrograms/l) and 5-fold increased in SF (7.8 vs 1.7 micrograms/l) compared to OA. The SF/plasma ratios for C5a, vitronectin and clusterin were 0.35, 0.36 and 0.23, respectively, not significantly different in the 2 diseases. CONCLUSION: SF terminal pathway activation in RA combined with low local levels of lysis inhibitors might allow lytic or sublytic attacks on local cells, resulting in inflammation and cell damage.

Arthritis, Rheumatoid↗
PubMed1999

Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease.

In this study complement activation and biosynthesis have been analysed in the brains of Huntington's disease (HD) (n = 9) and normal (n = 3) individuals. In HD striatum, neurons, myelin and astrocytes were strongly stained with antibodies to C1q, C4, C3, iC3b-neoepitope and C9-neoepitope. In contrast, no staining for complement components was found in the normal striatum. Marked astrogliosis and microgliosis were observed in all HD caudate and the internal capsule samples but not in normal brain. RT-PCR analysis and in-situ hybridisation were carried out to determine whether complement was synthesised locally by activated glial cells. By RT-PCR, we found that complement activators of the classical pathway C1q C chain, C1r, C4, C3, as well as the complement regulators, C1 inhibitor, clusterin, MCP, DAF, CD59, were all expressed constitutively and at much higher level in HD brains compared to normal brain. Complement anaphylatoxin receptor mRNAs (C5a receptor and C3a receptor) were strongly expressed in HD caudate. In general, we found that the level of complement mRNA in normal control brains was from 2 to 5 fold lower compared to HD striatum. Using in-situ hybridisation, we confirmed that C3 mRNA and C9 mRNA were expressed by reactive microglia in HD internal capsule. We propose that complement produced locally by reactive microglia is activated on the membranes of neurons, contributing to neuronal necrosis but also to proinflammatory activities. Complement opsonins (iC3b) and anaphylatoxins (C3a, C5a) may be involved in the recruitment and stimulation of glial cells and phagocytes bearing specific complement receptors.

Adult↗
PubMed1989

C5 neoepitopes appearing during activation.

After activation of serum complement, a neoantigen was reported to appear on a 54,000-dalton fragment of C5. On the other hand, a monoclonal antibody (MoAb), No. 568, revealed that an epitope on the beta-chain of C5 became masked after the formation of SC5b-9 complex. Murine MoAbs were obtained to human C5a-des-Arg. Some of them are specific only to C5a-des-Arg but not to C5a or C5. Using these MoAbs, a sandwich immunoassay was devised for detection and measurement of C5a-des-Arg. The neoepitopes for these MoAbs were analyzed by their reactivities to synthetic peptide derivatives of human and porcine C5a, and the structural changes of C5a were suggested to occur after the removal of the carboxyl terminal arginine residue.

Animals↗
PubMed2001

Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

Antibodies, Monoclonal↗
PubMed1988

Group B streptococci inhibit the chemotactic activity of the fifth component of complement.

Infection with group B streptococci (GBS) is associated with a poor acute inflammatory response in which neutrophils fail to localize at the site of invasion. In the present studies, we have examined the effects of group B streptococci on C-derived chemotactic activity in human serum. Fresh human serum was activated to form C5a and C5adesarg by incubation with zymosan. The activated serum was then incubated with group B organisms, centrifuged, and the supernatants tested for chemotactic activity for human polymorphonuclear leukocytes. Group B organisms caused a dose-dependent decrease in C-dependent chemotactic activity. The degree of inhibition was profound with 1 X 10(9) bacteria/ml (10% of control). Experiments indicated that significant chemotactic factor inactivation occurred within 2 min of exposure to GBS organisms, while maximal inhibition occurred after 30 min incubation. A number of different strains of GBS of types I, II, and III possessed inhibitory activity. In contrast, group D streptococci, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae failed to inhibit the C-derived chemotactic activity in human serum. Group A streptococci that were M protein positive also inactivated C-dependent chemotactic activity in serum, as previously reported. The inhibitory activity of the GBS strains could be abolished by heat or trypsin treatment but not by neuraminidase, pronase, or pepsin. C5a levels in zymosan-activated serum as measured by RIA were not decreased after incubation with an inhibitory strain suggesting that absorption was not involved. SDS-PAGE analysis revealed that group B streptococci degrade the C5a molecule, increasing its electrophoretic mobility by removing a fragment with a m.w. of approximately 650 Da. Thus, one of the reasons for the poor inflammatory response at the site of GBS infection may reside in the ability of these pathogens to inactivate C-derived inflammatory mediators. The GBS C5a-ase activity probably serves as an additional virulence factor for these organisms contributing to the poor inflammatory response characteristic of group B streptococcal infection.

Aminopeptidases↗
PubMed1995

Monoclonal antibodies directed against human C5 and C8 block complement-mediated damage of xenogeneic cells and organs.

The hyperacute rejection (HAR) of xenotransplanted organs is initiated by the deposition of natural antibodies on donor endothelium followed by the activation of the recipient complement system, which rapidly destroys the graft. Studies of the role of activated complement in HAR have suggested that natural antibody as well as early (C3a, C3b) and late (C5a, C5b-9) activated complement components may contribute to cell activation and damage. Attenuation of HAR has been achieved by blockade of C3 activation with soluble CR1 or consumptive depletion of complement with cobra venom factor; however, similar studies using specific inhibitors of terminal complement components have not been described. To address the contribution of C5a and the membrane attack complex (C5b-9, MAC) to complement-mediated xenogeneic cell and organ damage, we utilized functionally blocking monoclonal antibodies directed against the human terminal complement components C5 and C8. Our data show that both anti-C5 and anti-C8 mAbs protect porcine aortic endothelial cells from membrane damage mediated by human C5b-9. Additionally, both the anti-C5 and anti-C8 mAbs blocked complement-mediated generation of membrane prothrombinase activity on porcine aortic endothelial cells challenged with human serum. To test the ability of these antibodies to attenuate antibody and complement-mediated damage of xenogeneic organs, an ex vivo model was developed wherein isolated rat hearts were perfused with human serum in the presence or absence of the anti-C5 and anti-C8 mAbs. Our data demonstrate that mAbs directed against human C5 and C8 prevented organ damage by human serum complement and suggest that these molecules may serve as potent inhibitors of HAR.

Animals↗
PubMed2001

Contribution of anaphylatoxin C5a to late airway responses after repeated exposure of antigen to allergic rats.

We attempted to elucidate the contribution of complement to allergic asthma. Rat sensitized to OVA received repeated intratracheal exposures to OVA for up to 3 consecutive days, and pulmonary resistance was then estimated for up to 6 h after the last exposure. Whereas the immediate airway response (IAR) in terms of R(L) tended to decrease in proportion to the number of OVA exposures, late airway response (LAR) became prominent only after three. Although premedication with two kinds of complement inhibitors, soluble complement receptor type 1 (sCR1) or nafamostat mesylate, resulted in inhibition of the IAR after either a single or a double exposure, the LAR was inhibited after the triple. Premedication with a C5a receptor antagonist (C5aRA) before every exposure to OVA also inhibited the LAR after three. Repeated OVA exposure resulted in eosinophil and neutrophil infiltration into the bronchial submucosa which was suppressed by premedication with sCR1 or C5aRA. Up-regulation of C5aR mRNA was shown in lungs after triple OVA exposure, but almost no up-regulation of C3aR. Pretreatment with sCR1 or C5aRA suppressed the up-regulation of C5aR expression as well as cytokine messages in the lungs. The suppression of LAR by pretreatment with sCR1 was reversed by intratracheal instillation of rat C5a desArg the action of which was inhibited by C5aRA. In contrast, rat C3a desArg or cytokine-induced neutrophil chemoattractant-1 induced cellular infiltration into the bronchial submucosa by costimulation with OVA, but these had no influence on the LAR. These differences might be explained by the fact that costimulation with OVA and C5a synergistically potentiated IAR, whereas that with OVA and either C3a or cytokine-induced neutrophil chemoattractant-1 did not. C5a generated by Ag-Ab complexes helps in the production of cytokines and contributes to the LAR after repeated exposure to Ag.

Airway Resistance↗
PubMed1989

Demonstration of neutrophil chemotactic anaphylatoxins in human dandruff.

In contrast to scales collected from the scalps of nine healthy individuals where a few parakeratotic cells are observable, a large number of parakeratotic cells associated with some infiltrated polymorphonuclear leukocytes (PMNLs) were found in the scales obtained from 11 individuals complaining of dandruff. Therefore, we determined the neutrophil chemotactic properties of the water-soluble extracts of dandruff scales and normal control scalp scales. Aqeous extracts fractionated by Sephadex G-75 showed a potent chemotactic activity only in the fractions of the dandruff patients that eluted with cytochrome C marker (cyt C; molecular weight, 12 kDa). It was comparatively stable to heat but was greatly inhibited by the addition of anti-C5 antiserum. Radioimmunoassay demonstrated that, although small amounts of C5a and C4a anaphylatoxins were demonstratable even in the extracts of normal scalp, they were found in significantly increased amounts in the extracts of dandruff. Moreover, there was a significantly positive correlation between C5a and C4a concentrations in these extracts. These results suggest that classical complement pathway activation with resultant production of C5a anaphylatoxin is involved in the migration of PMNLs into the lesional skin of dandruff.

Adult↗
PubMed1985

Complement anaphylatoxins activity in middle ear effusion.

There are various theories on the causes of otitis media with effusion. The exact pathogenesis, however, still remains unknown, while the causes have been so far elucidated and studied by many researchers. This disease occurs frequently in children, showing an increasing trend, often causes subsequent deafness, and its treatment takes a long time causing social hardships. Therefore it is urgent to elucidate the pathogenesis of this disease. In this study the C3a and C5a fragments of complements from middle ear fluids, most closely related to the inflammatory reaction, were measured. The subjects were patients with otitis media with effusion consisting of 5 children and 9 adults. All cases showed retraction in the tympanic membrane findings, B type in the tympanogram classification, and serous type in the properties of middle ear fluids. CRP, alpha-1, alpha-2, beta-, gamma-globulin, neutrocytes, and lymphocytes in serum were normal when examined, and C3, C4, C3a, C5a, and CH50 were normal as well. Extremely high values of C3a and C5a in middle ear fluids were observed. The values of C3a were 18,000 ng/ml at maximum, 5,800 ng/ml at minimum, and 9,293 ng/ml on average. The values of C5a were 86, 20, and 55 ng/ml, respectively. No difference between childhood and adult cases was observed, in spite of differences in the underlying diseases among them. The above results revealed that an extremely intensive inflammatory reaction may take place in the middle ear, and that anaphylatoxin might play an important role as a delayed factor in otitis media with effusion.

Adult↗
PubMed1990

Complement activated leucopenia during hemodialysis: effect of pulse methyl-prednisolone.

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was withheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97-27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 micrograms/ml +/- SEM 33) and in patients off dialysis (177 micrograms/ml +/- 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.

Acute Kidney Injury↗
PubMed1997

Characterization of rat C5a anaphylatoxin receptor (C5aR): cloning of rat C5aR cDNA and study of C5aR expression by rat astrocytes.

Complement system activation within the central nervous system (CNS) is involved in demyelinating and neurodegenerative disorders, but the role of complement in the pathogenic process or in the repair remains unclear. Besides the direct lytic effects of complement on target cells (oligodendrocytes or neurons), complement can exert other functions through interaction of complement fragments with specific receptors. The C5a anaphylatoxin, an inflammatory peptide which is formed during complement activation, might play a role in the CNS pathogenesis, and activation and recruitment of glial cells by binding to its receptor (C5aR) on CNS cells. Using degenerate primers corresponding to homologous regions between human and mouse C5aR cDNAs, we have cloned a rat C5aR cDNA probe from rat monocytes RNAs after RT-PCR experiment. The rat C5aR probe isolated by this procedure allowed us to clone the rat C5aR cDNA-coding sequence using a library screening cloning strategy. This probe was also used to study the expression of the C5aR mRNA in the rat CNS. Northern blotting and RT-PCR experiments demonstrated the constitutive expression of C5aR mRNA in brain, spleen, kidney and lung. This transcript was also observed in primary culture of rat astrocytes. Microfluorimetry experiments demonstrated that C5aR expressed by astrocytes in culture is functional since the addition of C5a induced a dose-dependent increase of intracellular calcium concentration. The expression of the C5aR by astrocytes suggests new roles for the C5a anaphylatoxin in reactive astrogliosis to CNS injuries.

Amino Acid Sequence↗
PubMed1992

Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils.

Neutrophils activated by soluble particulate stimuli generate superoxide anion and subsequently form hydrogen peroxide and other oxygen radicals. The effect of hydrogen peroxide on the complement system in normal serum was investigated. Treatment of normal serum with hydrogen peroxide resulted in a diminution of the haemolytic activity of the total and alternative complement pathways and the haemolytic titres of C3 and C5 but not of C2, in normal serum. These decreases in complement activity depended on the concentration of hydrogen peroxide added to the serum. Immunoelectrophoretic analysis of hydrogen peroxide-treated serum showed that C3 and C5 proteins were activated. Complement degradation products C3a and C5a were produced in normal serum treated with hydrogen peroxide, and 20 mM EDTA abolished C3a and C5a production in hydrogen peroxide-treated serum but 20 mM Mg-EGTA did not. Catalase completely abolished and dimethylsulphoxide and D-mannitol, hydroxyl radical scavengers, partially inhibited the hydrogen peroxide-mediated complement activation. Hypochlorite, incubated with normal serum, significantly inhibited serum haemolytic activity, and sodium thiosulphate, a reducing agent, abolished the effect of hypochlorite. Normal serum incubated with activated neutrophils showed neutrophil chemotactic activity and decreased serum haemolytic activity, and the addition of catalase or methionine (5 mM) completely abolished the effects of activated neutrophils. These results suggest that hydrogen peroxide activates complement via an alternative pathway of complement activation and that hydroxyl radicals and other hydrogen peroxide-related species such as hypochlorite are most likely involved in hydrogen peroxide-mediated complement activation. Complement activation by oxygen radicals produced by activated neutrophils may be one of the mechanisms by which complement is activated in human immune complex diseases.

Complement Activation↗
PubMed1991

The role of the neutrophil in rheumatoid arthritis.

Neutrophils acquire lysosomal granules and assembly systems for producing soluble mediators of inflammation during the process of maturation in the bone marrow. Subsequently, they emigrate from the circulation when they become attracted to joint spaces of rheumatoid arthritis patients by chemoattractants such as the complement split product, C5a, and leukotriene B4. Exposure to immune complexes, rheumatoid factor, and cytokines in the synovial fluid results in neutrophil activation with release of granule contents, toxic oxygen metabolites, and proinflammatory products of the arachidonic acid cascade. This process is analogous to a local Arthus reaction in which activation of the complement system is a central event. Some of the inflammatory materials released by this reaction contribute to the cartilage destruction seen in rheumatoid arthritis. Because others are chemoattractants themselves, they perpetuate intraarticular inflammation and permit the predominance of acute inflammatory cells in lesions maintained by chronic inflammation.

Arthritis, Rheumatoid↗
PubMed2001

Inhibition of immune-complex mediated dermal inflammation in rats following either oral or topical administration of a small molecule C5a receptor antagonist.

1. Initiation of a peritoneal Arthus reaction by deposition of immune-complexes results in vascular leakage, polymorphonuclear leukocyte (PMN) infiltration, and tumour necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) production. We now demonstrate in rats that oral administration of the C5a receptor antagonist AcPhe[Orn-Pro-D-Cyclohexylalanine-Trp-Arg] (AcF-[OPdChaWR]; 1 - 10 mg kg(-1) 30 min prior to immune-complex deposition) inhibits these inflammatory markers in the peritoneal Arthus reaction. 2. Initiation of a dermal Arthus reaction resulted in a significant increase in vascular leakage, PMN infiltration, systemic production of TNFalpha and pathological changes in the dermis. 3. Pretreatment of rats with AcF-[OPdChaWR] either intravenously (1 mg kg(-1) 10 min prior to immune-complex deposition) or orally (1 - 10 mg kg(-1) 30 min prior to immune-complex deposition) significantly inhibited immune-complex mediated dermal vascular leakage and systemic cytokine production. Topical pretreatment with AcF-[OPdChaWR] (400 microg site(-1) in 10% dimethyl sulphoxide 10 min prior to immune-complex deposition) also inhibited vascular leakage, as well as histopathological changes associated with a dermal Arthus reaction. 4. Oral administration of 3 mg kg(-1) AcF-[OPdChaWR] resulted in the appearance of the drug in plasma within 5 min, with peak blood levels approximately 0.3 microM reached within 20 min. The plasma elimination half-life was approximately 70 min. The oral activity and bioavailability of AcF-[OPdChaWR], its activity when applied topically to the skin, suggest that small molecule C5a receptor antagonists may have therapeutic utility in dermal inflammatory disorders involving complement activation. 5. This is the first demonstration for either an orally or topically active C5a receptor antagonist, and suggests that small molecule C5a antagonists may have therapeutic utility when given by multiple routes of application.

Administration, Oral↗
PubMed1989

Cardiac anaphylaxis. Complement activation as an amplification system.

Complement is activated, and C3a and C5a anaphylatoxins are generated during hypersensitivity reactions clinically associated with cardiopulmonary collapse. The administration of C3a or C5a to nonsensitized isolated guinea pig hearts mimics the events caused by antigen challenge of sensitized hearts (i.e., cardiac anaphylaxis) in the absence of complement. Thus, complement-derived anaphylatoxins may participate in immediate hypersensitivity reactions in which the heart is a target organ. To assess the contribution of complement activation and anaphylatoxin generation to cardiac dysfunction, we have elicited anaphylaxis in isolated guinea pig hearts in the presence of complement and found that the ensuing dysfunction is markedly enhanced. This amplification is most likely attributable to anaphylatoxin formation because 1) inactivation of C3 or selective C3 depletion, i.e., the loss of the component responsible for the formation of the anaphylatoxins C3a and C5a, prevents complement-induced exacerbation of cardiac anaphylaxis, whereas reconstitution with C3 and C5, or even only C3, restores it; in fact, the greater the C3 content at the time of antigen challenge, the more intense the anaphylactic crisis; and 2) the severity of cardiac anaphylaxis is markedly reduced by preexposure to C3a, and this reduction is directly related to the dose of C3a injected and to the amount of endogenous cardiac histamine depleted by C3a before antigen challenge. Complement-derived anaphylatoxins appear to promote the same mediator release that has been initiated by the antigen-antibody reaction; thus, complement activation functions as an amplification system in cardiac anaphylaxis.

Anaphylatoxins↗
PubMed1999

In vivo evaluation of a phosphorylcholine coated cardiopulmonary bypass circuit.

A complete phosphorylcholine coated cardiopulmonary bypass circuit, including the Dideco D901 oxygenator, was tested for gas transfer, blood path resistance, and biocompatibility in a standardized setting. Blood compatibility was tested by measuring complement and platelet activation. Three dogs (mean body weight 28 +/- 3 kg) were placed on cardiopulmonary bypass at a flow rate of 600 mL/min during 6 hours. The animals were weaned from cardiopulmonary bypass and sacrificed electively after 7 days. Oxygen and carbon dioxide transfer were 26.6 +/- 2.4 mL/min and 33.0 +/- 1.9 mL/min, respectively. Mean pressure drop across the oxygenator was 52.6 +/- 0.2 mmHg. The respective baseline values for thromboxane B2, prostaglandin E2 and platelet factor 4 were 1817 +/- 283 pg/mL, 12783 +/- 2109 pg/mL, and 0.35 +/- 0.08 IU/mL. Thromboxane B2 and prostaglandin E2 increased slightly to 2881 +/- 868 pg/mL and 18083 +/- 3144 pg/mL at 30 minutes of bypass, whereas platelet factor 4 values remained stable curing the procedure. Concentrations of complement split products C5a were only mildly increased. After use scanning electron microscopy was performed on the inner housing, heat exchanger, and outer surface of the hollow fibers. No thrombi nor organized cellular deposits were found on any of the components. Phosphorylcholine coating of CPB seems to be very promising regarding platelet activation and complement activation.

Animals↗

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