1. |
- Borowiec, Jan, et al.
(author)
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Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass : A clinical study
- 1992
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In: Journal of Thoracic and Cardiovascular Surgery. - 0022-5223 .- 1097-685X. ; 104:3, s. 642-647
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Journal article (peer-reviewed)abstract
- Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.
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2. |
- Bagge, L., et al.
(author)
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Haemostasis at low heparin dosage during cardiopulmonary bypass with heparin-coated circuits pigs
- 1997
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In: Scandinavian Cardiovascular Journal. - 1401-7431 .- 1651-2006. ; 31:6, s. 275-281
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Review (other academic/artistic)abstract
- Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 +/- 6 IU/kg (mean +/- SEM) in group C and 100 +/- 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.
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3. |
- Borowiec, Jan, et al.
(author)
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Biocompatibility reflected by haemostasis variables during cardiopulmonary bypass using heparin-coated circuits
- 1997
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In: The thoracic and cardiovascular surgeon. - : Georg Thieme Verlag KG. - 0171-6425 .- 1439-1902. ; 45:4, s. 163-167
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Review (other academic/artistic)abstract
- Cardiopulmonary bypass (CPB) is associated with haemostatic disturbances and signs of acute inflammatory response, most likely related to poor biocompatibility of the artificial surfaces. Some haemostatic variables are known as markers of acute-phase reaction, blood cell trauma, and endothelial damage. The aim of the study was to evaluate the effect of heparin-coating of artificial surfaces on those variables of hemostasis. 14 patients operated on with elective coronary artery revascularization were randomized into two groups. In group H (n = 7), heparin-coated CPB circuits and in control group C (n = 7), noncoated CPB sets were used. Patients in group C received normal heparinization, e.g. bolus 300 IU/kg and additional doses to maintain activated coagulation time (ACT) over 400 sec during CPB. In group H, a bolus heparin dose was reduced by 25% (to 225 IU/kg) in order to compensate for the amount of heparin immobilized on circuit surfaces and the corresponding ACT limit was 300 sec. There were significant increases of the von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI) and tissue-plasminogen activator (tPA) starting at CPB end and rising to about twice the baseline levels postoperatively. This reaction was less evident in group H, as indicated by significantly lower levels of tPA compared to group C at CPB end (135% +/- 9 in group H versus 241% +/- 15 in group C, p < 0.0005) and at two hours postoperatively. The rates of tPA and vWF increase were lower in group H, also indicating reduced endothelial damage in this group. Marginally significant, a higher value of PAI was found in the C group early after CPB onset. Group H showed significantly lower concentrations of circulating complex between elastase and alpha 1-antitrypsin at CPB end and postoperatively, implicating a reduced granulocyte activation (60 min after protaminization 41 micrograms/L +/- 5 in group H versus 256 micrograms/L +/- 55 in group C, p < 0.05). It was concluded that the heparin-coated CPB circuits demonstrated improved biocompatibility which may be related to less disturbed haemostasis.
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4. |
- Borowiec, Jan, et al.
(author)
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Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose
- 1992
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In: Scandinavian journal of thoracic and cardiovascular surgery. - 0036-5580. ; 26:3, s. 177-185
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Journal article (peer-reviewed)abstract
- In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting.
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5. |
- Borowiec, Jan, et al.
(author)
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Effects of heparin-coating of cardiopulmonary bypass circuits on leukocytes during simulated extracorporeal circulation
- 1997
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In: Cardiovascular surgery. - 0967-2109 .- 1479-0653. ; 5:6, s. 568-573
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Review (other academic/artistic)abstract
- Heparin-coated circuits used during extracorporeal circulation reduce many postoperative complications occurring after heart surgery. Such complications are partly related to leukocyte activation with subsequent release of active substances, e.g. oxygen free radicals, myeloperoxidase and lactoferrin. This experiment was performed to elucidate a possible influence of heparin-coating on leukocytes. A 2-h-long simulated extracorporeal circulation was performed on two groups of five extracorporeal circulation circuits, primed with heparinized, fresh whole human blood and Ringer's solution. Heparin-coated circuits (HC group) were compared with uncoated circuits (NC group). Oxygen free radical production was estimated by determination of malonyldialdehyde in plasma and erythrocyte suspension. Granulocyte activation was measured in terms of myeloperoxidase and lactoferrin release. Time-related changes in leukocyte subset counts were analysed. Heparin-coating diminished myeloperoxidase and lactoferrin release. There were significant inter-group differences after 90 and 120 min of extracorporeal circulation for myeloperoxidase (101 (12) microg/l and 107(12) microg/l in the HC group versus 154(20) microg/l and 174(23) microg/l in the NC group), and after 120 min of extracorporeal circulation for lactoferrin (78(5) microg/l in the HC group versus 212(49) microg/l in the NC group). No significant changes of MDA concentration were observed in plasma or erythrocytes; however, a tendency towards lower MDA levels was seen after 90 and 120 min of extracorporeal circulation in the NC group. Neutrophil, monocyte and eosinophil numbers decreased significantly in the NC group but were unchanged in the HC group, as were lymphocyte counts. Heparin-coated extracorporeal circulation circuits significantly reduce granulocyte activation and better preserve the number of circulating neutrophils, eosinophils and monocytes, but do not change oxygen free radical production during simulated extracorporeal circulation.
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6. |
- Borowiec, Jan, et al.
(author)
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Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery : a clinical study
- 1992
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In: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 97:1, s. 55-66
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Journal article (peer-reviewed)abstract
- Cardiopulmonary bypass with systemic heparinization causes trauma to blood cells and coagulation defects. Artificial surfaces could be coated by end-linkage binding of heparin (Carmeda Bioactive Surface, CBAS). Use of such surfaces during cardiopulmonary bypass in animals resulted in less postoperative blood loss and better preservation of blood cells. In this study heparin-coated circuits were employed during coronary artery grafting in 7 patients (Group HC). Concomitantly, the heparin dose was reduced by 25% and an activated clotting time (ACT) of 300 sec was accepted. Additional 7 patients were operated with standard circuits (Group C), requiring ACT above 400 sec with normal doses of heparin. There were no thromboembolic complications in Group HC. The postoperative bleeding was generally low and without significant intergroup differences. Coagulation parameters displayed significantly lower ACT and anti-Factor Xa during bypass in Group HC. A tendency towards less blood cell trauma was observed with heparin-coated circuits. The protamine dose could be reduced by 50%, which significantly reduced the protamine/heparin quotient. This study indicates that routine cardiopulmonary bypass could be performed safely with heparin-coated circuits and reduced intravenous doses of heparin and protamine. It is suggested that the use of heparin-coated circuits may lead to less blood cell trauma.
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7. |
- Bozdayi, M., et al.
(author)
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Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen free radical production during coronary bypass surgery
- 1996
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In: Artificial Organs. - 0160-564X .- 1525-1594. ; 20:9, s. 1008-1016
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Journal article (peer-reviewed)abstract
- During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which can mediate reactions damaging tissue components. Blood contact with artificial surfaces during CPB leads to an activation of leukocytes, which are one of the sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte activation. In the present study, the heparin-coated circuits with noncoated cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar CPB sets (Group C). In each group, 8 patients were operated on for coronary revascularization. The release of granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin (LF) was evaluated. Production of OFR in the whole blood and in the granulocyte suspension were measured by chemiluminescence (CL). In both groups the whole blood CL declined during CPB. The whole blood CL induced by serum-opsonized zymosan, when enhanced by luminol, was significantly lower in Group HC at 45 min after CPB start (68 +/- 6% of initial values in Group HC vs. 87 +/- 6% in Group C, mean +/- SEM) and 30 min after protaminization (54 +/- 6% of initial values in Group HC vs. 72 +/- 6% in Group C, mean +/- SEM), and CL was significantly higher in Group HC at CPB end (83 +/- 5% of initial values in Group HC vs. 67 +/- 5% in Group C, mean +/- SEM) when enhanced by lucigenin. CL of isolated granulocytes showed no significant differences between the groups. Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were significantly lower in the heparin-coated CPB circuits.
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8. |
- Schiesser, S., et al.
(author)
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A Mild Synthesis of Aryl Triflates Enabling the Late-Stage Modification of Drug Analogs and Complex Peptides
- 2023
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In: Chemistry-a European Journal. - 0947-6539. ; 29:42
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Journal article (peer-reviewed)abstract
- We report the discovery of a straightforward protocol to convert phenols into the corresponding aryl triflates using 1-methyl-3-((trifluoromethyl)sulfonyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one in the presence of a fluoride source. This novel reagent can be handled without any precautions to exclude air or moisture making this method highly convenient. The reactions generally show very clean conversions within only a few minutes at room temperature. The mild conditions allow the so far unprecedented O-triflation of tyrosine in peptides bearing challenging side chains present for example in arginine and histidine including the late-stage triflation of complex bioactive peptides. We show how aryl triflates - an interesting but so far underutilized group - can be used to optimize physicochemical and in vitro properties of compound series in medicinal chemistry. We believe that this method is highly attractive for applications in peptide functionalization as well as automated and medicinal chemistry.
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