| 1. |
- Fosse, Erik, et al.
(författare)
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Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes : a European multicentre study
- 1997
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Ingår i: European Journal of Cardio-Thoracic Surgery. - 1010-7940 .- 1873-734X. ; 11:2, s. 320-327
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Moen, Oddvar, et al.
(författare)
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Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass
- 1997
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Ingår i: Annals of Thoracic Surgery. - 0003-4975 .- 1552-6259. ; 63:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The inflammatory response induced by cardiopulmonary bypass can result in severe organ dysfunction in some patients. This postperfusion response is caused mainly by contact between blood and the foreign surface of the cardiopulmonary bypass equipment and includes adhesion of leukocytes to vascular endothelium, which precedes a series of events that mediate inflammatory damage to tissues. METHODS: Low-risk patients accepted for coronary artery bypass grafting were randomized to operation with the cardiopulmonary bypass surface either completely heparin coated (Duraflo II) or uncoated. There were 12 patients in each group. Blood plasma sampled during cardiopulmonary bypass was analyzed for complement activation (C3bc and terminal SC5b-9 complement complex) and neutrophil activation (lactoferrin and myeloperoxidase). In addition, neutrophils, monocytes, and platelets were counted, and the expression of surface markers on the neutrophils and monocytes (complement receptor [CR] 1, CR3, CR4, and L-selectin) and on the platelets (P-selectin and CD41) was quantified with flow cytometry. RESULTS: Clinical and surgical results were similar in both groups. In the group with the heparin-coated surface, the formation of the terminal SC5b-9 complement complex was significantly reduced, and the counts of circulating leukocytes and platelets were significantly less reduced initially but were higher at the end of cardiopulmonary bypass compared with baseline. Also, the expression of CR1, CR3, and CR4 was significantly less upregulated and the L-selectin, significantly less downregulated on monocytes and neutrophils. CONCLUSIONS: We conclude that heparin coating reduces complement activation and attenuates the leukocyte integrin and selectin response that occurs when uncoated circuits are used.
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| 3. |
- Moen, Oddvar, et al.
(författare)
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Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility
- 1996
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 62:4, s. 1134-1140
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Centrifugal pumps are being used increasingly for short-term extracorporeal circulation purposes such as during heart operations. Whether the centrifugal pump improves the cardiopulmonary bypass biocompatibility has not been fully documented. METHODS: A roller pump (n = 20) was compared in vivo with a centrifugal pump (n = 20) in groups of patients in which cardiopulmonary bypass circuits that were either totally heparin coated (Carmeda BioActive Surface; n = 20) or uncoated (n = 20) were used. We expected the heparin coating to attenuate blood activation, thus possibly making the comparison of the two pumps easier with respect to their different blood activation potentials. Samples of blood plasma, obtained during cardiopulmonary bypass from low-risk coronary artery bypass grafting patients, were analyzed for hemolysis (plasma haemoglobin), complement activation (C3bc and the terminal complement complex), a complement lytic inhibitor (vitronectin), coagulation activation (fibrinopeptide A), granulocyte activation (lactoferrin), and platelet activation (beta-thromboglobulin). RESULTS: The concentrations of terminal complement complex, lactoferrin, and beta-thromboglobulin were significantly lower in association with heparin-coated surfaces. The concentration of plasma hemoglobin was significantly lower in association with the centrifugal pump. In uncoated circuits, the beta-thromboglobulin level was significantly higher in association with the roller pump than with the centrifugal pump, but this significant reduction in the beta-thromboglobulin level did not hold true for the heparin-coated circuit group. CONCLUSIONS: A heparin-coated cardiopulmonary bypass surface reduces the blood activation potential during cardiopulmonary bypass, and the centrifugal pump causes less hemolysis than the roller pump.
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| 4. |
- Moen, Oddvar, et al.
(författare)
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Differences in blood activation related to roller/centrifugal pumps and heparin-coated/uncoated surfaces in a cardiopulmonary bypass model circuit
- 1996
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Ingår i: Perfusion. - : SAGE Publications. - 0267-6591 .- 1477-111X. ; 11:2, s. 113-123
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Tidskriftsartikel (refereegranskat)abstract
- An in vitro model cardiopulmonary bypass (CPB) circuit consisting ot tubing, oxygenator and venous reservoirs with either a roller or a centrifugal pump, and with either heparin-coated (Carmeda Bioactive Surface, CBAS) or uncoated surfaces, was studied with respect to 'blood activation', using small-scale-based blood volume (450 + 500 ml). Sixteen circuits were tested in each pump group, eight with and eight without heparin-coated surfaces, by circulating heparinized fresh human blood for 72 hours at 30 degrees C. Blood plasma, sampled at defined intervals, was analysed for haemolysis (lactate dehydrogenase and potassium), complement activation (C3bc and C5b-9 (TCC)), complement lytic inhibitors (vitronectin and clusterin), coagulation activation (fibrinopeptide A), granulocyte (lactoferrin and myeloperoxidase) and platelet (beta-thromboglobulin) activation and contaminating endotoxin. The heparin coating significantly reduced the concentrations of C3bc, TCC, fibrinopeptide A, lactoferrin, myeloperoxidase and beta-thromboglobulin. The two pump types did not differ with respect to these parameters, but the roller pump caused significantly higher increases in plasma LDH and potassium and significantly greater reductions in clusterin and vitronectin than the centrifugal pump. Endotoxin concentration was low at the start and after 24 hours in all groups. These results confirm that heparin-coated CPB surfaces reduce blood activation, and suggest that centrifugal pumps cause less haemolysis and less reduction in lytic complement inhibitors than roller pumps.
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| 5. |
- Moen, Oddvar, et al.
(författare)
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Disparity in blood activation by two different heparin-coated cardiopulmonary bypass systems
- 1995
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Ingår i: Annals of Thoracic Surgery. - 0003-4975 .- 1552-6259. ; 60:5, s. 1317-1323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several studies have indicated reduced "blood activation" in heparin-coated cardiopulmonary bypass systems. The present study compares the effect of two different heparin coatings on different blood activation indices. METHODS: Low-risk patients (n = 40) were randomized to coronary artery bypass grafting using cardiopulmonary bypass with surfaces coated entirely by either the Duraflo II heparin coat or the Carmeda Biological Active Surface, or with identical uncoated equipment. In all cases, a standard systemic heparin dosage was used. Complement activation (C3 activation products C3bc and C3a and formation of fluid phase terminal SC5b-9 complement complex), neutrophil activation (lactoferrin and myeloperoxidase), and lytic inhibitors (vitronectin and clusterin) were quantified during cardiopulmonary bypass and 6 hours postoperatively. RESULTS: Heparin coating by either method reduced the formation of terminal SC5b-9 complement complex and the release of lactoferrin and myeloperoxidase compared with uncoated systems. Lactoferrin and myeloperoxidase levels increased significantly during cardiopulmonary bypass in the Duraflo II group, whereas no significant increase was observed in the Carmeda Biological Active Surface group. The least formation of terminal SC5b-9 complement complex and neutrophil activation was observed with the Maxima Carmeda Biological Active Surface-coated equipment. The vitronectin and clusterin concentrations were significantly less reduced in the Duraflo II compared with the control group. This study underlines the importance of terminal SC5b-9 complement complex as a suitable marker in the evaluation of complement activation during cardiopulmonary bypass. CONCLUSIONS: Both heparin coatings reduce blood activation, probably more so with Carmeda Biological Active Surface than with Duraflo II.
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| 6. |
- Övrum, Eivind, et al.
(författare)
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Complement and granulocyte activation in two different types of heparinized extracorporeal circuits
- 1995
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - 0022-5223 .- 1097-685X. ; 110:6, s. 1623-1632
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Tidskriftsartikel (refereegranskat)abstract
- Complement and granulocyte activation were studied in cardiopulmonary bypass circuits completely coated with either end-attached covalent-bonded heparin, the Carmeda BioActive Surface, or with the Duraflo II bonded heparin, in combination with reduced systemic heparinization (activated clotting time > 250 seconds). The control groups were perfused with uncoated circuits and full heparin dose (activated clotting time > 480 seconds). Altogether 67 patients undergoing elective first-time myocardial revascularization were investigated, having extracorporeal perfusion with a Duraflo II coated circuit (n = 17), an identical but uncoated circuit (n = 17), a Carmeda coated circuit (n = 17), or an equivalent uncoated circuit (n = 16). During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c (C3bc) and the terminal SC5b-9 complemented complex increased markedly in all four groups compared with baseline, but significantly less in the two coated groups than in their control groups. Additionally, a significantly lower concentration of C3bc was observed in the Carmeda coated group, with maximal increase of median 28 AU/ml compared with 50 AU/ml in the Duraflo II coated group (p = 0.003). Similarly, in the Carmeda coated group, the maximal increase of terminal complement complex was considerably lower (0.8 AU/ml) than the levels recognized in the Duraflo II coated group (2.4 AU/ml) (p < 0.001). The release of the granulocyte activation myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of bypass. A significant reduction of lactoferrin release was recognized when comparing the coated groups with the control groups. The difference between the two coated groups (Carmeda 228 micrograms/L; Duraflo II 332 micrograms/L; p = 0.05) was marginally significant. For myeloperoxidase, no significant differences were observed between the coated and uncoated groups. In conclusion, both types of heparin-coated circuits reduced complement activation and release of lactoferrin, but the Carmeda circuit proved to be more effective than the Duraflo II equipment.
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| 7. |
- Övrum, Eivind, et al.
(författare)
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Complete heparin-coated cardiopulmonary bypass and low heparin dose reduce complement and granulocyte activation
- 1996
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Ingår i: European Journal of Cardio-Thoracic Surgery. - 1010-7940 .- 1873-734X. ; 10:1, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- Complete heparin-coated extracorporeal circuits, including cardiotomy reservoir, have recently become available for routine cardiac surgery. The effects on complement and granulocyte activation using a heparin-coated circuit in combination with reduced systemic heparinization (activated clotting time (ACT) > 250 s) were studied in 33 patients undergoing elective first time myocardial revascularization. The patients were prospectively randomized either to a heparin-coated group (Group H, n = 17), or to a control group (Group C, n = 16) treated with an identical uncoated circuit and full heparin dose (ACT > 480 s). During cardiopulmonary bypass (CPB) the C3 activation products C3b, iC3b, and C3c (C3bc) and the terminal SC5b-9 complement complex (TCC) increased markedly in both groups compared to baseline, but to a much lesser extent in the heparin-coated group. The maximal increase of C3bc during the operation was a median of 28 arbitrary units (AU)/ml in the heparin-coated group, compared to 45 AU/ml in the control group (P = 0.01). Similarly, in Group H the maximal increase of TCC was significantly lower (median 0.8 AU/ml) than the levels recognized in Group C (median 1.9 AU/ml) (P < 0.0001). The release of the granulocyte activation enzymes lactoferrin and myeloperoxidase also increased during CPB in both groups compared to baseline level. The maximal increase of lactoferrin concentration was a median of 229 micrograms/l in Group H and significantly lower than 647 micrograms/l in the control group (P = 0.0002). As for myeloperoxidase, there were no significant intergroup differences. In conclusion, a complete heparin-coated circuit and low systemic heparinization for CPB in coronary artery surgery were associated with reduced activation of the complement system and less release of lactoferrin. The results indicate improved biocompatibility of this option for extracorporeal circulation.
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