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A Sturk

Publications and source records attributed to A Sturk.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Preeclampsia not (yet) predictable from the blood platelet count].

Platelet activation plays an important role in the pathogenesis of pre-eclampsia as demonstrated by reduced platelet count, increased mean platelet volume and elevated plasma concentrations of beta-thromboglobulin and platelet factor 4 in pre-eclamptic patients. Thrombocytopenia precedes the onset of clinical symptoms of pre-eclampsia. Possibly an enhanced activation state of the platelets in the circulation is present some time before the onset of pre-eclampsia: platelet activation might then be used to predict pre-eclampsia. Flow cytometry is considered the most sensitive technique at this moment to measure the activation of platelets. Fluorescent-labelled antibodies are used to detect antigens that appear on the platelet surface or change their conformation upon activation. During the first and second trimester of pregnancy pre-eclamptic patients have an increased expression of some antigens on the surface of their platelets, such as CD63. There is no reliable platelet test yet to predict the onset of pre-eclampsia.

Adult↗
PubMed1999

Proinflammatory cytokines and elastase-alpha-1-antitrypsin in Argentine hemorrhagic fever.

Argentine hemorrhagic fever (AHF) is a disease caused by Junin virus. In the acute phase, patients present hematologic and neurologic involvement with high levels of interferon-alpha and tumor necrosis factor-alpha (TNF-alpha. Nineteen patients with a confirmed diagnosis of AHF were studied: six severe, four moderate and nine mild cases. Serum levels of interleukin-6 (IL-6), IL-6 soluble receptor (IL-6sR), IL-8, IL-10, and elastase-alpha1-antitrypsin complex (E-alpha 1AT) were assayed by ELISAs. Levels of IL-6, IL-8, and IL-10 were high in nine, 12, and 13 patients, respectively, while levels of IL-6sR were high in two patients and low in one patient. Seven patients had increased levels of E-alpha1AT. Significant correlations were found between levels of both IL-8 and IL-10 with those of TNF-alpha as well as between IL-8 and E-alpha 1AT. These data demonstrate activation of pro-inflammatory and anti-inflammatory cytokine pathways, and statistical analysis showed differences among the clinical forms of illness. This study shows that IL-8 plays an essential role in neutrophil activation in AHF patients as demonstrated in other infectious diseases.

Cytokines↗
PubMed1999

Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions.

Factor VIII activity (factor VIII:C) levels > or =150 IU/dl are associated with a 5- to 6-fold increased risk of venous thrombosis compared to levels <100 IU/dl, and fibrinogen levels > or =5.0 g/l increase the thrombosis risk 4-fold. These high levels are present in 25% resp. 3% of the patients with a first episode of venous thrombosis. These findings were based on measurements after the thrombotic event, so the factor VIII and fibrinogen levels in thrombosis patients may have been influenced by acute phase reactions or ongoing inflammatory responses. In the present study we measured plasma C-reactive protein (CRP) as a sensitive marker of an acute phase reaction in 474 thrombosis patients and 474 age- and sex-matched healthy controls, that were part of the Leiden Thrombophilia Study (LETS). Mean and median CRP levels were higher in thrombosis patients than in the controls, suggesting inflammation in some patients. CRP affected both factor VIII and fibrinogen levels, in patients and controls alike. After adjustment for the effect of CRP, high factor VIII:C levels still increased the thrombosis risk 6-fold and high fibrinogen levels 4-fold, which is for both very similar to the risk before correction for CRP levels. These results show that although systemic inflammation may be present in some of the patients, elevated levels of factor VIII:C and fibrinogen were in general not caused by acute phase reactions. This further supports a causal relationship between both high factor VIII:C and fibrinogen levels and venous thrombosis.

Acute-Phase Reaction↗
PubMed1998

Determination of tumour necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation.

Ex vivo production of cytokines as determined by whole blood stimulation and supernatant ELISA is partly determined by heritability. To assess the ability of this system to distinguish between high and low producers the laboratory error and individual variation were investigated. Whole blood samples from healthy volunteers were collected using endotoxin-free tubes and were incubated with 0 to 1000 ng/ml lipopolysaccharide concentrations for 4 and 24 h, and subsequently centrifuged. In the supernatants, TNF-alpha and IL10 were measured by ELISA. Coefficients of variation for the day-to-day variation in the blood sampling, transport and stimulation as well as in the whole blood stimulation per se ranged from 7.5% to 12.3%. The intra-individual variation was 15% (TNF-alpha) and 19% (IL10) in contrast to the inter-individual variation of, on average, 35%. No interchanging of ranks between high and low producers was observed after repeating the whole blood stimulation on distinct days. The whole blood stimulation system is able to distinguish high and low producers of TNF-alpha and IL10.

Blood↗
PubMed1998

Disappearance of glycoprotein Ib from the platelet surface in pericardial blood during cardiopulmonary bypass.

OBJECTIVES: Several investigators have reported decreased expression of glycoprotein Ib on the platelet surface during coronary artery bypass grafting, but others could not confirm this finding. Because platelet glycoprotein Ib functions as an adhesion receptor for von Willebrand factor and other adhesive proteins, this decreased expression may explain excessive postoperative blood loss. In this study the expressions of glycoprotein Ib and other platelet activation markers were studied in the systemic and pericardial blood of seven patients undergoing coronary artery bypass grafting. Pericardial blood was recently shown to have high activation levels of fibrinolytic and coagulation pathways; we hypothesized that this local blood activation might be paralleled by extensive platelet activation and associated disappearance of glycoprotein Ib. METHODS: Expression of platelet surface antigens was determined by whole-blood double-label flow cytometry. RESULTS: Glycoprotein Ib expression in systemic blood decreased 10% (p = 0.03) from preoperative levels at the start of cardiopulmonary bypass and 30% (p = 0.04) before release of the aortic crossclamp. Expression in pericardial blood at these times decreased by 50% and 51%, respectively (p = 0.003, p = 0.009). No changes were observed in the expression of the platelet activation antigens CD62P (P-selectin, indicating platelet alpha-granular release) and CD63 (indicating lysosomal release) or in binding of monoclonal antibody PAC-1 (detecting the fibrinogen-binding receptor conformation of the glycoprotein IIb-IIIa complex). CONCLUSION: Glycoprotein Ib disappeared from the platelet surface during bypass grafting, most notably in pericardial blood. No increased expression of CD62P, CD63, or PAC-1 was found, indicating the absence of general platelet activation.

Aged↗
PubMed1998

Lorenzo's oil and platelet activation in adrenomyeloneuropathy and asymptomatic X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal beta-oxidation, which results in accumulation of very long-chain fatty acids, causing damage to the nervous system, adrenal cortex and testis. The two most frequent phenotypes are childhood cerebral adrenoleukodystrophy (CCALD) and adrenomyeloneuropathy (AMN). Some affected males demonstrate no clinical signs (asymptomatic ALD), whereas female carriers can also be affected. Patients with X-ALD have been treated with Lorenzo's oil, a 4:1 combination of oleic acid and erucic acid, with thrombocytopenia as the main side effect and sometimes leading to a hemorrhagic diathesis. We studied platelet count, size and membrane surface exposure of platelet activation antigens in 17 adult X-ALD patients. Eight patients used the prescribed amount of erucic acid (as glyceroltrierucate) or more (very compliant), five used less(compliant), and four did not use the diet. All eight very compliant patients had highly enlarged platelets and seven manifested thrombocytopenia. An enhanced in vivo platelet activation status was established by increased platelet surface expression of P-selectin (CD62P, PADGEM, GMP-140) in five of the seven thrombocytopenic patients, and of increased fibrinogen receptor exposure (measured with the antibody PAC-1) in three of these five patients. The other nine compliant or untreated patients had normal platelet counts and, generally, normal P-selection and fibrinogen receptor expression. A diet-induced 7- to 27-fold enrichment of erucic acid was observed in the platelets of the four patients studied. We conclude that the thrombocytopenia in AMN patients using Lorenzo'soil is associated with circulating platelets that have an increased erucic acid content, size and activation status. We hypothesize that the erucic acid in some way induces the increased size and thus, directly or indirectly, increased platelet activation or instability in vivo. This then causes the thrombocytopenia, with circulating platelets representing a population that has not yet been sufficiently changed to be removed, but has clear signs of activation.

Journal Article↗
PubMed1997

Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant.

BACKGROUND: Microparticles from platelets and other cells have been extensively studied and characterized in vitro. Although the level of platelet-derived microparticles is elevated in a variety of diseases, including cardiac surgery, virtually nothing is known about their functions in vivo. The aim of the present study was to investigate the procoagulant properties of microparticles generated in vivo. METHODS AND RESULTS: In 6 patients at the end of cardiopulmonary bypass, 14.8 x 10(9)/L (median; range, 9.7 to 27.4 x 10(9)/L) platelet-derived microparticles were present in pericardial blood, whereas blood obtained from the systemic circulation contained 1.6 x 10(9)/L (median; range, 0.4 to 8.9 x 10(9)/L) of such microparticles, as determined by flow cytometry. Microparticles stained positively for phosphatidylserine as determined with labeled annexin V. In contrast to systemic blood, pericardial blood contained not only microparticles of platelet origin but also microparticles that originated from erythrocytes, monocytes, or granulocytes, and other hitherto unknown cellular sources. Plasma prepared from pericardial blood and to a lesser extent plasma from systemic blood obtained at the same time, stimulated formation of thrombin in vitro. This activity of pericardial plasma was lost after removal of its microparticles by high-speed centrifugation, whereas the corresponding microparticle pellet was strongly procoagulant. The generation of thrombin in vitro involved a tissue factor/factor VII-dependent and factor XII-independent pathway. CONCLUSIONS: This study is the first to demonstrate that microparticles generated in vivo can stimulate coagulation.

Annexin A5↗
PubMed1997

[Laboratory testing virtually centralized to benefit both patients and drug research].

Laboratory analyses in multicentre safety studies of new drugs usually are performed in central laboratories outside the Netherlands. Patient care requires local (hospital) laboratory tests. In the so-called Virtually Centralized Laboratory the Dutch local laboratories report their results after data communication and data transformation in such a way that they seem to form one laboratory. The local analytical results are transformed by calibrating the local methods using standard preparations, thus reducing the inter laboratory variation. This concept may lead to one set of national reference values for all general clinical chemical and haematological laboratory tests.

Blood Chemical Analysis↗
PubMed1997

Can flow cytometric detection of platelet activation early in pregnancy predict the occurrence of preeclampsia? A prospective study.

OBJECTIVES: An increased platelet activation status is present in patients with preeclampsia. Our purpose was (1) to establish by means of flow cytometry whether platelets circulate in an activated state during the first and second trimesters of pregnancy and (2) to establish whether early platelet activation predicts the onset of preeclampsia. STUDY DESIGN: Consecutively, 244 pregnant women were included in a prospective study design. Platelets in whole blood samples from the pregnant women in the first trimester, the second trimester, and after delivery were labeled with the following antibodies associated with platelet activation: anti-CD62P (P-selectin, alpha-granule secretion), anti-CD63 (GP53, lysosomal secretion), anti-CD31 (GPIIa', platelet endothelial cell adhesion molecule-1). The surface antigen exposure was determined by double-label flow cytometry with anti-CD42b (GPIb, a platelet-specific monoclonal glycoprotein) to select platelets and platelet-derived materials. Preeclampsia was defined as a diastolic blood pressure > or = 90 mm Hg and proteinuria > or = 0.3 gm in a 24-hour urine sample (International Society for Study of Hypertension in Pregnancy criteria). RESULTS: Seventeen of 244 patients had preeclampsia (6.9%). Only first-trimester CD63 expression had an area under the curve > 0.5 by receiver-operator characteristic curve analysis and was selected as a possible predictor of preeclampsia. We found a sensitivity of 47% and a specificity of 76% with use of a percentage of activated platelets above 2% as a positive test. Likelihood ratios were 1.94 for positive likelihood and 0.69 for negative likelihood. Univariate logistic regression analysis results were odds ratio 2.8 (95% confidence interval 1.0 to 7.6). Multivariate logistic regression analysis results were odds ratio 2.9 (95% confidence interval 0.92 to 8.9). However, the odds ratio of first antenatal diastolic blood pressure was two to four times higher than the odds ratio of first-trimester CD63 expression. The combination of first-trimester CD63 and first antenatal diastolic blood pressure increases the positive likelihood ratio from 1.94 to 9.4, with a sensitivity of 41%, a specificity of 96%, and a negative likelihood ratio of 0.62. CONCLUSIONS: Increased first-trimester CD63 expression is an independent risk factor for development of preeclampsia. CD63 expression might be useful to identify a subgroup of patients with a high risk for development of preeclampsia, especially in combination with first-trimester antenatal diastolic blood pressure. This method of patient selection may enable more efficient intervention studies in patients at risk than do the selection methods used so far.

Antigens, CD↗
PubMed1997

Extensive platelet activation in preeclampsia compared with normal pregnancy: enhanced expression of cell adhesion molecules.

OBJECTIVES: Platelets play an important role in the pathophysiologic mechanisms of preeclampsia. Our purpose was to investigate by means of flow cytometry to what extent platelets circulate in an activated state during normal pregnancy and whether this activation is more extensive in preeclampsia. STUDY DESIGN: Platelets in whole blood from 10 preeclamptic third-trimester pregnant women (highest diastolic blood pressure range 100 to 130 mm Hg, proteinuria range 0.59 to 11.5 gm/24 hr) and from 10 normotensive third-trimester pregnant controls were analyzed with the following activation markers: anti-P-selectin (alpha-granule secretion), anti-CD63 (lysosomal secretion), PAC-1 (monoclonal antibody against fibrinogen receptor conformation of the glycoprotein IIb/IIIa complex), anti-platelet endothelial cell adhesion molecule-1, and annexin-V (a placental protein that binds to negatively charged phospholipids, present on the outside of the platelet plasma membrane after activation). The differences in surface antigen exposure between the two groups were determined by double-label flow cytometry. Flow cytometric data were analyzed in two ways: first, the percentages of activated platelets above a certain threshold compared with a nonpregnant control sample were determined, indicative for activation of a subpopulation of cells, and, second, the mean fluorescence intensities were determined, indicative of the mean surface antigen expression of the total platelet population. RESULTS: Analysis of the percentage of activated platelets proved most informative. With this analysis an enhanced platelet activation status was present in 4 of 10 normotensive patients and a more extensive platelet activation status in all 10 preeclamptic patients, as indicated by P-selectin (p = 0.008) and CD63 (p = 0.03) expression. Increased platelet endothelial cell adhesion molecule-1 (p = 0.005) expression was also observed in preeclampsia. CONCLUSIONS: Flow cytometric analysis clearly indicated that platelets circulate in a more extensively activated state during preeclampsia than during normal pregnancy. The increased platelet endothelial cell adhesion molecule-1 expression in preeclamptic patients demonstrates that, besides alpha-granular and lysosomal release, other hitherto unknown mechanisms are involved. Platelet endothelial cell adhesion molecule-1 appears to be the best marker to distinguish preeclamptic patients from normotensive pregnant women. Only a subpopulation of the platelets appears to be activated.

Adult↗
PubMed1997

Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations.

OBJECTIVE: Heparin coating reduces complement activation on the surface of extracorporeal circuits. In this study we investigated its effect on activation of the contact system in 30 patients undergoing coronary artery bypass grafting with the use of a heparin-coated (Duraflo II, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.; n = 15) or an uncoated extracorporeal circuit (n = 15). METHODS: Plasma markers that reflect activation of contact (kallikrein-C1-inhibitor complexes), coagulation (prothrombin fragments F1 + 2), or fibrinolytic (plasmin-alpha 2-antiplasmin complexes) systems were determined before and during the operation. The generation of kallikrein-C1-inhibitor complexes was reduced by 62% (p = 0.06) after the onset of cardiopulmonary bypass and by 43% (p = 0.026) after the cessation of bypass in the group in which a heparin-coated circuit was used compared with the group in which the circuit was uncoated. Generation was reduced by 58% (p = 0.06) when the ratio of kallikrein-C1-inhibitor to prekallikrein after onset of bypass was considered. We detected significant increases in F1 + 2 levels in both groups and increases in plasmin-alpha 2-antiplasmin complexes in the heparin-coated group at cessation of bypass, but no intergroup differences were observed. Thus use of heparin-coated extracorporeal circuits during cardiac operations reduces formation of kallikrein-C1-inhibitor complexes when compared with use of uncoated circuits. The heparin coating is not accompanied by similar reductions in coagulation or fibrinolysis, suggesting that thrombin and plasmin formation during cardiopulmonary bypass occurs mainly independently of the contact system activation.

Aged↗
PubMed1997

Activated protein C resistance--a major risk factor for thrombosis.

Resistance to activated protein C is a recently detected phenomenon that has gained a rapid acceptance as a major risk factor for venous thromboembolism. The phenotypic expression of resistance to activated protein C is characterized by a poor response to the anticoagulant activity of activated protein C, a key enzyme in the down-regulation of blood coagulation, which causes a disposition for a hypercoagulable state. At least 90% of the cases with resistance to activated protein C are explained by a point mutation in the gene for coagulation factor V, resulting in replacement of an Arg to Gln at position 506 (factor V:Q506, often denoted factor V Leiden), one of the three activated protein C cleavage sites in activated factor V. The mutation is inherited as an autosomally dominant trait and has a prevalence of 2% to more than 10% in the general Caucasian population. A number of clinical studies, using different inclusion criteria, show a prevalence of activated protein C resistance of 20-60% among patients with venous thromboembolism. The actual thrombotic risk is moderate with an odds ratio of 5-7 but its high prevalence makes it by far the most important inherited risk factor known today, even higher than the sum of contributions from inherited deficiencies of antithrombin, protein C and protein S. Recent data suggest that activated protein C resistance, which is not due to factor V:Q506 and which appears to be acquired, is also a risk factor for venous thrombosis and for cerebral ischaemic disease. A decreased response to activated protein C is common during pregnancy and during use of oral contraceptives, but the clinical relevance of these findings have yet to be determined. The activated protein C resistance phenotype is typically diagnosed with an activated partial thromboplastin time-based assay, which detects factor V:Q506-dependent as well as acquired activated protein C resistance. However, the sensitivity and specificity for the factor V mutation are usually below 90%. Coagulation instruments with a turbidimetric or photometric clot detection principle generally provide a better performance as compared to electromechanical instruments. The activated partial thromboplastin time test requires careful control of preanalytical variables and platelet contamination should be below 1% since otherwise a falsely low activated protein C response will be obtained. A sensitivity and specificity of close to 100% for factor V:Q506 is obtained in a modified activated partial thromboplastin time test using predilution of sample plasma with factor V deficient plasma. The influence of preanalytical variables in this assay is minor. A number of polymerase chain reaction-based methods, some of them allele-specific, have been published, which provide convenient and objective confirmation of the factor V mutation. Thrombotic events are often triggered through the presence of a combination of inherited and circumstantial risk factors. The high prevalence of activated protein C resistance raises the issue whether it would be cost-beneficial to screen for this trait in connection with surgery, pregnancy and oral contraceptives. Some data already support this, but prospective studies will be necessary to delineate under which circumstances this might be implicated.

Antiphospholipid Syndrome↗
PubMed1997

Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons.

Patients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, IL-1beta, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1beta (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 microg IL-6 x kg body-weight(-1) x day(-1) showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.

Acute-Phase Reaction↗
PubMed1996

Ligand-dependent enhancement of human antithrombin gene expression by retinoid X receptor alpha and thyroid hormone receptor beta.

We studied potential modulators of antithrombin gene expression. A putative hormone response element (HRE) was identified by sequence similarity analysis of the antithrombin promoter, situated between nucleotides -92 and -54 relative to the transcription start site. This HRE contains three hexa-nucleotide motifs with an AGGTCA consensus, which are potential targets of members of the steroid/thyroid superfamily of nuclear receptors. Stimulation of the hepatoma cell line HepG2 with the receptor ligands L-3,5,3'-tri-iodothyronine, all-trans retinoic acid, or their combination, increased production of antithrombin into the culture medium by 1.3-, 1.6-, and 2.0-fold, respectively. In contrast, the receptor ligand 1,25-dihydroxy-cholecalciferol[1,25-(OH)2VitD3] did not influence antithrombin production. Analysis of promoter chloramphenicol acetyl-transferase (CAT) constructs, showed that the first 86 bp of the antithrombin promoter region are sufficient for basal transcription. The DNA length polymorphism of 32 bp or 108 bp, located upstream of position -276, did not influence anti-thrombin promoter activity. The antithrombin promoter activity dropped to background values when deleting the region -97/-49 of promoter fragment -453/+57. Transactivation of the antithrombin promoter by retinoid X receptor alpha (RXR alpha) (5-7-fold) or thyroid hormone receptor beta (TR beta) (4-5-fold) was only observed when at least -167/+57 bp of the promoter region is present in CAT constructs, and when the appropriate ligand of the nuclear receptor was added. This transactivation was not observed upon deletion of the antithrombin promoter region -97/-49. With three copies of the antithrombin promoter fragment -109/-42 in front of the thymidine kinase minimal promoter, transactivation was only obtained with RXR alpha, and not with TR beta. In conclusion, these results indicate that the ligand-dependent enhancement of antithrombin gene expression is regulated by RXR alpha as well as by TR beta. Transactivation of antithrombin gene expression by RXR alpha and TR beta appears to be dependent upon the presence of promoter region up to nucleotide -167. The HRE segment (-109/-42) only confers RXR alpha responsiveness to a heterologous promoter. Further study is needed to unravel the exact nature of this HRE and its 5'-flanking sequences.

Antithrombin III↗
PubMed1996

Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia.

OBJECTIVE: The aim of this study was to determine whether the increase in post-operative oxygen consumption (delta VO2) in cardiac surgery patients is related to endotoxemia and subsequent cytokine release and whether delta VO2 can be used as a parameter of post-perfusion syndrome. DESIGN: Prospective study. SETTING: Operating room and intensive care unit of a university hospital. PATIENTS: Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids. MEASUREMENTS AND RESULTS: Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high delta VO2 (> or = median value of the entire group) were compared with measurements from patients with low delta VO2 (< median). Patients with high delta VO2 had higher levels of circulating endotoxin (P = 0.004), TNF (P = 0.04) and IL-6 (P = 0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low delta VO2. Several hours after delta VO2 the patient's body temperature rose. Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of delta VO2. CONCLUSIONS: This study demonstrates that patients with high post operative oxygen consumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.

Adult↗
PubMed1996

Circulating endothelin in cardiac operations: influence of blood pressure and endotoxin.

BACKGROUND: Endothelin is involved in the control of cardiovascular and renal functions and acts as a neuromodulator. METHODS: In a prospective study among 15 male patients who underwent coronary artery bypass grafting, we investigated the release pattern and possible stimuli of circulating endothelin. RESULTS: We detected a steep increase in endothelin concentrations after the onset of cardiopulmonary bypass (CPB), and a second minor increase during CPB. The steep increase in endothelin concentrations correlated with the change in arterial pressures at the onset of CPB (r = -0.57; p < 0.03). The slow increase in endothelin concentrations during CPB, however, correlated with mean endotoxin levels during and after CPB (r = 0.60; p < 0.02). CONCLUSIONS: The change in arterial pressure at the onset of CPB seems to induce a steep and fast increase in circulating endothelin level, which is probably mediated through the baroreceptors. The slow increase in endothelin level during CPB is associated with increased circulating endotoxin concentration. It may be that either endothelin-mediated vasoconstriction induces endotoxin transmigration from the intestine or endotoxin stimulates secretion from endothelial cells.

Aged↗
PubMed1996

Low-dose and high-dose aprotinin improve hemostasis in coronary operations.

Prophylactic aprotinin therapy has become a popular method to reduce bleeding associated with cardiac operations. Today essentially two dose regimens are used, a high-dose regimen with administration throughout the complete operative procedure and a low-dose regimen with administration only during bypass. In unblinded studies both regimens were found to be equally effective. This double-blind placebo-controlled study in 115 patients undergoing elective coronary artery bypass grafting was done to confirm these results without potential investigator bias. Intraoperative hemoglobin loss was significantly reduced (p < 0.01) by 42% in the high-dose group and by 17% in the low-dose group compared with loss in control subjects. Blood loss 6 hours after operation was 377 ml in the low-dose and 266 ml in the high-dose group compared with 630 ml in the placebo group (p < 0.05 and p < 0.001, respectively). The average number of transfusions with packed red blood cells was reduced 31% in the low-dose group and 45% in the high-dose group, but the reductions were not significant. In a subgroup of patients, markers for coagulation and fibrinolysis were studied to investigate whether a different extent of activation existed. Fibrinolysis as measured by D-dimer levels was completely inhibited by the high-dose regimen, but was only partly suppressed in the low-dose group as compared with findings in the placebo group. Thrombin generation during cardiopulmonary bypass as reflected by F1 + 2 levels was lower in patients treated with aprotinin, but the difference was not significant. Concentrations of thrombin inactivated by antithrombin III were not different between the groups. The observation that low-dose aprotinin significantly improved hemostasis but did not inhibit hyperfibrinolysis supports our previous finding that low-dose aprotinin mainly protects platelet adhesive function. The better result obtained with high-dose aprotinin may indicate the contribution of hyperfibrinolysis to bleeding after cardiopulmonary bypass. Because high-dose aprotinin is administered outside the period of full heparinization and might therefore increase the risk of thromboembolic complications, we propose a modification of the low-dose schedule to increase aprotinin levels sufficient for plasmin inhibition before release of the aortic crossclamp.

Antithrombin III↗