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Biomedical subjects

V Videm

Publications and source records attributed to V Videm.

At least 37 records · Page 2Linked to original sources
PubMed1999

Platelet compatibility of an artificial surface modified with functionally active heparin.

Platelet compatibility after coating an artificial material with functionally active heparin was investigated. Blood was circulated in uncoated or heparin coated PVC tubing. In one hour platelet counts decreased from 155 (113-184)x10(9)/l to 124 (100-148)x10(9)/l with uncoated compared to 164 (132-192)x10(9)/l with heparin coated tubing (intergroup p = 0.02). Beta-thromboglobulin increased from 116 (80-148) microg/l to 1039 (757-1298) microg/l with uncoated and to 352 (229-638) microg/l with heparin coated tubing (intergroup p = 0.005). Platelet counts and beta-thromboglobulin correlated closely with complement activation. Solid-phase enzyme immunoassay demonstrated substantial deposition of CD42a/GPIbIX and CD61/GPIIIa on uncoated, but not on heparin coated tubing (intergroup p<0.0005). Scanning electron microscopy demonstrated activated platelets and aggregates on uncoated in contrast to heparin coated tubing, where scattered, unactivated platelets were found. Changes in P-selectin and microparticles were minor. In conclusion, this heparin surface substantially improved platelet compatibility. Markers of choice for in vitro evaluation were platelet counts, beta-thromboglobulin and platelet deposition.

Antigens, CD↗
PubMed1999

Effect of anti-C5a antibody on blood-lung and blood-brain barrier in rabbits after decompression.

The complement activation product C5a may be an important mediator of tissue injury after decompression stress. This study investigated whether the administration of anti-C5a antibody may reduce changes after decompression in the lung and in the brain. Two groups of rabbits were used; one receiving anti-C5a monoclonal antibody (n = 7) and the other receiving a sham antibody as control (n = 7) before pressure exposure. Five rabbits (4 in the anti-C5a group and 1 in the control group) died during the 2-h observation period postdive due to massive bubbling. Polymorphonuclear leukocyte (PMN) infiltration of lung tissue and pulmonary edema was observed, but this accumulation was unaffected by anti-C5a pretreatment. However, a significant positive correlation was observed between PMN accumulation and survival time postdive. Brain-specific gravity was lower for the group treated with anti-C5a antibody compared to the control group. Further, it was lower for those rabbits that died early compared to the ones that survived the 2-h period. This study was unable to prove a protective effect on the blood-brain and blood-lung barrier by injecting anti-C5a antibody. A possible beneficial effect of anti-C5a antibody may be masked by the mechanical damage caused by the gas bubbles.

Animals↗
PubMed1998

Heparin coating reduces cell activation and mediator release in an in vitro venovenous bypass model for liver transplantation.

We used an in vitro model for venovenous bypass in a prospective, randomized study to analyze the effect on leukocytes cell activation after coating the total blood contact surface with covalently bound heparin. In ten experiments heparin-coated circuits were used, and in ten other experiments noncoated circuits were used. Monocyte cytokine production and neutrophil myeloperoxidase release were analyzed. Monocytes were isolated using anti-CD14 paramagnetic beads, and oligo (dT)25 beads were used to isolate mRNA before subsequent reverse transcription and semiquantitative amplification of various cytokines in order to determine time-related changes in expression during bypass. After 2 h, mRNAs for IL-1 beta and IL-6 were highly upregulated in noncoated compared to heparin-coated circuits. Little or no change was seen in the expression of other cytokines. IL-1 beta and IL-6 were measured in plasma after 12 h and reflected the upregulated mRNAs in noncoated circuits. A significantly reduced release of myeloperoxidase was observed in coated versus noncoated circuits. This indicates that heparin-coated surfaces reduce cellular activation and the release of inflammatory mediators.

Anticoagulants↗
PubMed1998

Immunoglobulin prolongs survival of pig kidneys perfused ex vivo with human blood.

Intravenous immunoglobulin (IVIG) (Octagam), was used to determine the effect on hyperacute rejection in an ex vivo xenograft model. Six pig kidneys were perfused with IVIG and fresh human AB blood, and six control pig kidneys were simultaneously perfused with albumin and blood from the same donation. The survival of the IVIG-perfused xenografts (median, 6.5 h) was significantly (P = 0.03) longer than the albumin-perfused xenografts (median, 3.5 h). Complement was activated in both groups. The administration of IVIG to the perfused blood resulted in immediate and significantly higher complement activation in the fluid phase as compared with the albumin group. At rejection the fluid phase complement activation was higher in the IVIG group than in the albumin group for C1rs/C1inh complexes, C4bc, Bb and TCC. At the time of rejection both the albumin and the IVIG group demonstrated interstitial tubular haemorrhage, vasculitis or necrosis of glomerular capillaries and glomerular microthrombi. IgM, C1q, C3c, C4 and fibrin were located in arteries and glomeruli and IgG in the interstitium in both groups at rejection. The fluid phase findings are consistent with a modulatory effect of IVIG on complement activation by deviating the classical pathway activation towards the fluid phase. The prolonged survival of the IVIG-perfused kidneys suggests that IVIG may be useful to dampen hyperacute rejection.

Animals↗
PubMed1998

Leucocyte filtration during cardiopulmonary bypass hardly changed leucocyte counts and did not influence myeloperoxidase, complement, cytokines or platelets.

In some patients, coronary artery bypass surgery induces postoperative organ dysfunction despite an apparently adequate revascularization and good haemodynamic performance. This complication may be caused by activation of the body's inflammatory systems on blood contact with large foreign surfaces in the extracorporeal circuit. Activated leucocytes may play an important role in organ damage, and it is conceivable that leucocyte removal by filtration may decrease the potential side-effects of cardiopulmonary bypass (CPB). The aim of the present study was to investigate possible effects of leucocyte filtration during the whole CPB period in elective coronary artery bypass surgery on biochemical and clinical parameters. Forty patients were randomized to extracorporeal circulation using a leucocyte-depleting filter (group L, n = 20) or to extracorporeal circulation with no leucocyte filter (group C, n = 20). In the leucocyte-depleted group, the mean total white blood cell counts increased from 6.3 (95% confidence interval, 5.5-7.0) x 10(9)/l to 7.0 (5.7-8.3) x 10(9)/l during extracorporeal circulation and in the control group from 6.3 (5.2-7.3) x 10(9)/l to 8.5 (7.2-9.8) x 10(9)/l. The intergroup difference was not statistically significant (p = 0.84). A substantial increase in concentrations of interleukin-6, myeloperoxidase and complement activation products were observed in both groups without statistically significant intergroup differences. It is concluded that the leucocyte-depletion filter did not cause a significant reduction of circulating white blood cells during CPB, and there were no significant differences between the groups with respect to the inflammatory markers studied.

Aged↗
PubMed1997

Extracorporeal membrane oxygenation using a centrifugal pump and a servo regulator to prevent negative inlet pressure.

BACKGROUND: We studied whether negative inlet pressure created by a centrifugal pump during extracorporeal membrane oxygenation damages blood. METHODS: Fresh, whole human blood and primer were circulated through a test circuit, applying an inlet pressure of 0, -50, or -100 mm Hg. Thereafter, hemolysis and kidney function were compared between 6 patients treated before and 14 patients treated after inclusion in our setup of extracorporeal membrane oxygenation with a servo inlet pressure regulator. RESULTS: In vitro, negative inlet pressure caused substantial hemolysis, leukocyte and platelet destruction, and complement activation. Maximal plasma free hemoglobin concentrations were 199 mg/100 mL before use of the servo inlet pressure regulator and 40 mg/100 mL afterward (p = 0.06), and serum creatinine peaked at 330 and 115 mumol/L, respectively (p = 0.03). The minimal 24-hour diuresis normalized for weight was 4.8 mL/kg before use of the servo inlet pressure regulator and 45.6 mL/kg afterward (p = 0.03). Three of 5 evaluable patients before use of the servo inlet pressure regulator and 1 of 14 patients after inclusion in this setup experienced anuria (p = 0.04). CONCLUSIONS: There were strong indications that reduction of negative pump inlet pressure with the servo regulator prevented hemolysis and kidney damage.

Complement Activation↗
PubMed1997

Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study.

OBJECTIVE: This study was carried out to: (a) compare complement and granulocyte activation during cardiac operations in patients operated with cardiopulmonary bypass coated with heparin by the Duraflo II method, with activation in patients operated with uncoated circuits; and (b) relate complement, and granulocyte activation to selected adverse effects. METHODS: In a multicentre study among Rikshospitalet, Ullevaal Hospital in Norway and Uppsala University Hospital in Sweden, plasma concentrations of the complement activation products C4b/iC4b/C4c (C4bc), C3b/iC3b/C3c (C3bc), the terminal SC5b-9 complement complex (TCC), and the granulocyte proteins myeloperoxidase and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass. Seventy-six patients underwent surgery operated with circuits coated by the Duraflo II heparin coating and 75 uncoated circuits. The same amount of systemic heparin was administered to all patients. RESULTS: In both groups a significant increase in C4bc was first seen by the end of operation, from 86.7 +/- 12.5 to 273.0 +/- 277.4 nM in controls and from 86.9 +/- 18.5 to 320.2 +/- 190.5 nM in the control group, confirming previous documentation that the classical pathway is not activated during CPB, but as a consequence of protamin administration. The formation of C4bc did not differ significantly between the two groups. In the uncoated group the C3bc concentration increased from 124.0 +/- 15.3 to a maximum of 1176.1 +/- 64.7 nM (P < 0.01) and in the coated group it increased from 129.8 +/- 16.1 to a maximum of 1019.4 +/- 54.9 nM (P < 0.01) during CPB. Summary values but not peak values differed significantly between the groups. In the uncoated group the TCC concentration increased from 0.52 +/- 0.03 to a maximum value of 8.09 +/- 0.57 AU/ml (P < 0.01) while in the coated group the TCC concentration increased from a baseline of 0.53 +/- 0.03 to a peak value of 5.2 +/- 0.24 AU/ml (P <0.01). The difference between the peak values was statistically significant (P = 0.00002). In both groups a significant increase in myeloperoxidase and lactoferrin release was observed by the end of operation. There was no difference in myeloperoxidase or lactoferrin release between the two groups. TCC levels were compared to the occurrence of perioperative infarction, development of lung or renal failure, postoperative bleeding, time on ventilator and days in hospital. Three patients developed perioperative infarction; the peak levels of TCC were significantly higher in these patients than in the 148 patients that did not develop infarction. The reduction in TCC formation in the heparin-coated group was not associated with differences in any of the other clinical parameters. Few adverse effects occurred in the study. The peak values of C3bc were higher in the patients needing inotropic support that in those who did not, the relevance of this finding remains uncertain. CONCLUSION: It is concluded that the Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes. No certain correlation was established between complement and granulocyte activation and clinical outcome.

Aged↗
PubMed1997

Effects on complement, granulocytes and platelets of a leukocyte-depletion filter during in vitro extracorporeal circulation.

In an in vitro study, extracorporeal circuits equipped with either a leukocyte-depleting filter (n = 5) or a standard arterial-line filter (n = 5) were perfused for 120 minutes with fresh human whole blood. Leukocyte activation, leukocyte and platelet counts and complement activation were studied. Significant reduction of leukocyte and platelet counts and significant activation of leukocytes and of platelets were found in both groups, but without significant intergroup difference for any parameter after 120 minutes of perfusion. The leukocyte-depleting filters, however, were somewhat more effective in removing leukocytes during the initial 30 minutes of circulation.

Complement System Proteins↗
PubMed1996

Heparin in clinical doses 'primes' granulocytes to subsequent activation as measured by myeloperoxidase release.

The author pre-incubated isolated human granulocytes with increasing doses of heparin (0-100 IU/mL) before subsequent stimulation with formyl-met-leu-phe. There was a dose-dependent increase in granulocyte activation as measured by myeloperoxidase release, quantitated in enzyme-immunoassay. This 'priming' effect of heparin was not due to activation of contaminating platelets or to endotoxin, and there was no reduction in granulocyte viability. Heparin-induced 'priming' of granulocytes may be clinically relevant in the setting of cardiopulmonary bypass. The author describes a sensitive and specific double antibody enzyme-immunoassay for myeloperoxidase from human granulocytes, with an inter-assay coefficient of variation of 12.6%, an intra-assay coefficient of variation of 4.3%, and a lower detection limit of 1.8 microg/l.

Cardiopulmonary Bypass↗
PubMed1995

High and low heparin dose with heparin-coated cardiopulmonary bypass: activation of complement and granulocytes.

BACKGROUND: Cardiopulmonary bypass with heparin-coated circuits allows reduced amounts of systemic heparin. Heparin inhibits activation of the complement cascade experimentally, but the effects of different levels of systemic heparin on activation of complement and granulocytes in patients have remained unknown. METHODS: Fifty-two patients undergoing coronary artery bypass procedures were studied. Cardiopulmonary bypass circuits completely coated with surface-bound heparin were used for one group given low-dose heparin (n = 17) (activated clotting time > 250 seconds), and was compared with a second group having normal high-dose heparin (activated clotting time > 480 seconds) (n = 18). A third control group was perfused with ordinary uncoated circuits and a full heparin dose (n = 17). RESULTS: During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c increased markedly in all three groups compared with baseline, but significantly less in the two heparin-coated groups (high dose, median maximal increase 58 arbitrary units (AU)/mL; low dose, 48 AU/mL) compared with the uncoated control group (74 AU/mL) (p < 0.01). The difference between the two coated groups was not significant. Similarly, the maximal increase in terminal SC5b-9 complement complex was considerably lower in the heparin-coated groups (high dose, 2.5 AU/mL; low dose, 2.6 AU/mL) compared with the level observed in the uncoated control group (5.3 AU/mL) (p < 0.01). The release of the granulocyte activation enzymes myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of cardiopulmonary bypass (p < 0.01). The concentration of lactoferrin was significantly (p < 0.01) reduced in the low heparin dose group compared with the two other groups receiving normal high heparin doses, indicating that circulating heparin is an important granulocyte agonist, acting independently of the presence or absence of heparin-coated surfaces. Also for myeloperoxidase a higher level was observed in the high heparin dose group. CONCLUSIONS: Complement activation was significantly reduced in both heparin-coated groups and was independent of the level of systemic heparinization, whereas granulocyte activation was reduced only in patients who received low doses of systemically administered heparin. The results indicate that a moderate reduction of the systemic heparin dose may be an advantage with regard to improved biocompatibility when using heparin-coated cardiopulmonary bypass circuits.

Adult↗
PubMed1994

Human complement activation by polygeline and dextran 70.

The complement cascade is activated during cardiopulmonary bypass (CPB) and in trauma victims. In order to study whether plasma expanders may contribute to complement activation in these settings, fresh human serum was incubated with dextran 70 and polygeline. C3-activation products and the terminal complement complex (TCC) were quantified in enzyme immunoassays. At 37 degrees C, dextran caused immediate, dose-dependent C3 activation and TCC formation with decline later in the rate of TCC formation relative to serum-saline controls. High doses of polygeline caused slight activation after 15-30 min. The authors tested also the activation under conditions comparable to those found during clinical CPB. Activation induced by dextran and polygeline was increased by dilution of the serum. Furthermore, the plasma expanders counteracted the well-known inhibitory effects of heparin (4 IU/ml) and moderate hypothermia (30 degrees C) on complement activation. The authors conclude that dextran, and to a lesser extent polygeline, may contribute to complement activation during CPB and other clinical settings such as shock treatment.

Cardiopulmonary Bypass↗
PubMed1993

A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding.

A recombinant peptide encoding the CD11b A domain bound 54Mn2+ with a high affinity. Other divalent cations, including Mg2+, Zn2+, Ni2+, Co2+, and Cd2+, but not Ca2+ or Ba2+, competed effectively for Mn2+ binding. Amino acid substitutions within two conserved and noncontiguous regions in the recombinant peptide abolished 54Mn2+ binding. When these substitutions were introduced independently in complement receptor type 3 (CR3), each abolished the metal-dependent binding of the receptor to the major C3 opsonin iC3b, without impairing subunit association or surface expression of the receptor. These findings identify an unsuspected and novel metal-binding site within the A domain of CR3 that is required for metal-dependent ligand binding and also identify a good target for designing drugs aimed at countering the inflammatory potential of this key receptor.

Amino Acid Sequence↗
PubMed1993

Calprotectin and complement activation during major operations with or without cardiopulmonary bypass.

Plasma concentrations of the granulocyte cell marker calprotectin were assessed during operation and 24 hours postoperatively in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass, abdominal aneurysmectomy with implantation of an aortic graft, or thoracotomy without implantation of synthetic material. The concentration of calprotectin increased significantly (p < 0.01) in all three groups. Ten of the 30 patients in the group undergoing cardiopulmonary bypass received methylprednisolone at the start of the operation. No difference in calprotectin concentration was seen between the two subgroups (p > 0.05). Plasma concentration of calprotectin was shown to increase rapidly in patients undergoing cardiopulmonary bypass and aneurysmectomy, in whom complement activation also took place. However, the calprotectin concentration increased slowly during the operation and the postoperative period in patients undergoing a thoracotomy, in whom complement was not activated. At wound closure the calprotectin concentration was significantly elevated in the cardiopulmonary bypass and aneurysmectomy groups compared with the thoracotomy group (p < 0.05). The calprotectin concentration remained elevated during the postoperative period in all three groups. Our results indicate that calprotectin may serve as a suitable cellular marker when the biocompatibility of artificial surfaces is studied.

Adult↗
PubMed1992

Time for new concepts about measurement of complement activation by cardiopulmonary bypass?

Fifty-one patients admitted for routine coronary bypass operations were randomized to cardiopulmonary bypass with a membrane oxygenator (Capiox) or a bubbler (Polystan or William Harvey). Complement activation was measured using enzyme immunoassays for concentrations of C3 activation products and the terminal complement complex. From 5.8 to 8.1 arbitrary units (AU)/mL (medians), the plasma concentrations of C3 activation products increased by 119.9 AU/mL (Capiox), 124.6 AU/mL (Polystan), and 79.5 AU/mL (William Harvey) to a peak at closure of the sternum (not significant when related to baseline concentrations). The increase in C3 activation products and baseline C3 activation were linearly correlated (R2 = 0.30; p less than 0.0001). From 5.5 to 6.1 AU/mL, the plasma terminal complement complex concentrations increased by 45.2 AU/mL (Capiox), 15.4 AU/mL (Polystan), and 17.4 AU/mL (William Harvey) to a peak before termination of cardiopulmonary bypass. Maximal terminal (C5-C9) activation was significantly higher in the membrane oxygenator group (p less than 0.0001) and showed no relationship to C3 activation. Measurement of C3 activation only gives no information about C5-C9 activation. At present, terminal complement complex quantitation is probably the best index of C5-C9 activation during cardiopulmonary bypass.

Cardiopulmonary Bypass↗
PubMed1992

Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations.

Complement activation after cardiopulmonary bypass is correlated with postoperative organ dysfunction. Heparin coating of the entire blood-contact surface of the cardiopulmonary bypass circuit has proved to reduce complement activation in vitro. A membrane oxygenator and tubing setup coated with functionally active heparin was compared with an uncoated, otherwise identical setup in 20 patients undergoing routine coronary bypass operations. The concentrations of C3 activation products and the terminal complement complex were measured in sensitive and specific enzyme immunoassays. Peak concentrations of C3 activation products were 90.1 (74.7 to 107.4) AU/ml (medians and 95% confidence intervals) and 52.4 (35.7 to 76.4) AU/ml with the uncoated and coated setups, respectively (p = 0.02). The corresponding concentrations of the terminal complement complex were 26.2 (20.1 to 37.5) AU/ml and 13.7 (11.1 to 25.1) AU/ml (p = 0.03). Blood loss from the mediastinal drains during the first 12 postoperative hours was 533 (416 to 975) ml in patients treated with the uncoated setup and 388 (313 to 579) ml in the coated treatment group (p = 0.06) and was significantly correlated with peak concentrations of the terminal complement complex (p = 0.01). There were no differences in neutrophil counts nor platelet numbers between the treatment groups. The approximate 45% reduction in complement activation with the heparin-coated cardiopulmonary bypass device indicates a substantial improvement of biocompatibility.

Aged↗