Biomedical subjects

M Dentener

Publications and source records attributed to M Dentener.

7 recordsLinked to original sources

PubMed2002

Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery.

This study investigated the relationship of the hepatosplanchnic production and uptake of inflammatory mediators, hepatosplanchnic perfusion, and outcome during major abdominal surgery to evaluate the hypothesis that regional production of inflammatory mediators precedes the development of hepatic dysfunction. This retrospective analysis of data and blood samples collected during a randomized controlled clinical trial included high-risk surgical patients undergoing major abdominal surgery in a 24-bed university-afilliated intensive care unit. Patients were divided into a subgroup that developed hepatic dysfunction (HD+) postoperatively and a subgroup without hepatic dysfunction (HD-). Hepatic vein and arterial plasma levels of IL-6, IL-8, s-E-selectin, s-ICAM-1, and the TNF-receptors 55 and 75 were measured, and the flux was calculated by multiplying the difference in hepatic vein minus arterial levels of the mediators by the hepatosplanchnic flow. Systemic (thermodilution) and total hepatosplanchnic blood flow (using indocyanine green [ICG]-dilution method) and gastric intramucosal pH (pHi) were assessed preoperatively, 4, 24, and 36 h postoperatively. Of a total of 26 patients, 6 patients developed hepatic dysfunction after their abdominal surgery (mean 6 days postoperatively). The number of sepsis-related deaths and postoperative days on the ventilator were significantly higher in this group. A higher production of IL-8, TNF-receptor-75 and 55 in the hepatosplanchnic area in the HD+ subgroups was found, which preceded the development of organ dysfunction (P = 0.04, P = 0.02, and P = 0.02, respectively). Moreover, the uptake of s-ICAM-1 was significantly increased in this subgroup. Furthermore, total hepatosplanchnic blood flow was significantly higher and pHi was significantly lower in the HD+ group, whereas global hemodynamic data were similar in the two subgroups. In conclusion, the development of postoperative organ dysfunction is preceded by an increased regional inflammatory response, indicated by an increased soluble TNF-receptor shedding and IL-8 production from the hepatosplanchnic area together with an increased uptake of s-ICAM-1. Moreover, an increased total hepatosplanchnic blood flow with intramucosal acidosis was associated with this regional inflammatory response.

Aged↗

PubMed2001

Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy.

BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status. METHODS: Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result. RESULTS: Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.

Acute-Phase Proteins↗

PubMed1999

Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery.

STUDY OBJECTIVES: This study was conducted to investigate whether intraoperative blood transfusions affect the release of proinflammatory mediators in patients undergoing cardiac surgery. Therefore, we measured plasma levels of bactericidal permeability increasing protein (BPI) as a marker of neutrophil activation, interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), and C-reactive protein (CRP). In addition, these mediators, except CRP, were also measured in packed red cell units (PCs) administered to these patients. DESIGN: Prospective study. SETTING: Cardiopulmonary surgery department in a university hospital. PATIENTS: One hundred fourteen consecutive patients undergoing cardiac surgery. INTERVENTIONS: Blood samples were taken at induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and at 0.5, 4, 8, and 18 h thereafter. RESULTS: Thirty-six patients received PC intraoperatively. BPI levels in patients who received transfusions were significantly higher at 0.5 and 4 h after aortic unclamping than in patients without transfusions (p < 0.05), and increased with the number of PC administered. IL-6 levels at 0.5, 4, and 18 h after aortic unclamping were also significantly higher in patients who received transfusions (p < 0.01). BPI was found in all units of packed red cells tested at concentrations up to 15 times preoperative plasma levels in patients. However, PC IL-6 could be detected in none of the samples. Plasma levels of LBP and CRP were similar in both patient groups. LBP was found in very low concentrations in all PC. Patients who received intraoperative transfusions had a worse postoperative performance. CONCLUSIONS: Intraoperative PC transfusions do contribute to the inflammatory response after cardiac surgery both by enhancing part of the response and by directly changing plasma concentrations of inflammatory mediators. Furthermore, these data show that intraoperative PC transfusion is associated with a worse postoperative performance.

Acute-Phase Proteins↗

PubMed1998

Systemic inflammation present in patients undergoing CABG without extracorporeal circulation.

STUDY OBJECTIVES: This study was conducted to evaluate to what extent the cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response. Therefore, we measured bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin 6 as inducer of the acute phase response, and lipopolysaccharide binding protein and C-reactive protein as parameters of the acute phase response in patients undergoing CABG either with or without the use of CPB. DESIGN: Prospective study. SETTING: Cardiopulmonary surgery department in a university hospital. PATIENTS: Sixteen patients undergoing elective CABG were included. Eight patients underwent surgery with CPB, and eight patients underwent surgery without CPB (non-CPB). INTERVENTIONS: In the CPB group, blood samples were taken upon induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h thereafter. In the non-CPB group, blood samples were taken upon induction of anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft anastomoses. MEASUREMENTS AND RESULTS: BPI release from neutrophil granules markedly increased during surgery in CPB patients but not in non-CPB patients. The increase in acute phase reactants, however, was the same in both patient groups. CONCLUSIONS: These data indicate that the acute phase response in CABG patients, which has historically been ascribed to the CPB procedure, is predominantly caused by the surgical procedure per se. Early neutrophil activation, however, is seen only when extracorporeal circulation is used.

Acute-Phase Proteins↗

PubMed1997

Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans.

To determine the role of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-induced inflammation, 12 healthy subjects received an intravenous injection with LPS (2 ng/kg) preceded by infusion of either a recombinant human dimeric TNF receptor type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6) from -30 minutes to directly before LPS injection. LPS elicited a transient increase in plasma TNF activity, peaking after 1.5 hours (219 +/- 42 pg/mL; P < .05). Infusion of TNFR:Fc completely neutralized endogenous TNF activity. LPS administration was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator, plasminogen activator activity, and plasmin-alpha2-antiplasmin complexes), followed by inhibition (plasma plasminogen activator inhibitor type I), changes that were completely prevented by TNFR:Fc. By contrast, TNFR:Fc did not influence LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes). TNFR:Fc strongly inhibited endothelial cell activation (plasma levels of soluble E-selectin), modestly reduced neutrophil responses (neutrophilia and plasma concentrations of elastase-alpha1-antitrypsin complexes and lactoferrin), but did not affect the release of secretory phospholipase A2 or lipopolysaccharide-binding protein (P > .05). Infusion of TNFR:Fc only (without LPS) in another 6 normal subjects did not induce any inflammatory response. These data indicate that TNF is involved in only some inflammatory responses to intravenous LPS in humans.

Adult↗

PubMed1997

Epinephrine exerts anticoagulant effects during human endotoxemia.

To determine the effect of a physiologically relevant elevation in the plasma concentrations of epinephrine on the activation of the hemostatic mechanism during endotoxemia, 17 healthy men were studied after intravenous injection of lipopolysaccharide (LPS, 2 ng/kg), while receiving a continuous infusion of epinephrine (30 ng/kg/min) started either 3 h (n = 5) or 24 h (n = 6) before LPS injection, or an infusion of normal saline (n = 6). Activation of the coagulation system (plasma concentrations of thrombin-antithrombin III complexes and prothrombin fragment F1+2) was significantly attenuated in the groups treated with epinephrine when compared with subjects injected with LPS only (P <0.05). Epinephrine enhanced LPS-induced activation of fibrinolysis (plasma levels of tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes; P <0.05), but did not influence inhibition of fibrinolysis (plasminogen activator inhibitor type I). In subjects infused with epinephrine, the ratio of maximal activation of coagulation and maximal activation of fibrinolysis was reduced by >50%. Hence, epinephrine exerts antithrombotic effects during endotoxemia by concurrent inhibition of coagulation, and stimulation of fibrinolysis. Epinephrine, whether endogenously produced or administered as a component of treatment, may limit the development of disseminated intravascular coagulation during systemic infection.

Adult↗

PubMed1997

Release of lipopolysaccharide toxicity-modulating proteins in patients undergoing cardiopulmonary bypass using noncoated and heparin-coated extracorporeal circuits. A clinical pilot study.

STUDY OBJECTIVE: Cardiopulmonary bypass (CPB) induces a generalized inflammatory response, including activation of leukocytes, contributing to postoperative morbidity. The inflammatory pathways leading to this systemic inflammatory response syndrome are considered identical to those involved in septic shock. Therefore, we studied the release of bactericidal/permeability-increasing protein (BPI), lipopolysaccharide binding protein (LBP), and soluble CD14 (sCD14)-all proteins that modulate the effects of lipopolysaccharide (LPS)-in patients undergoing CPB. In addition, the effect of heparin coating of the extracorporeal bypass circuit on the release of these parameters was assessed. DESIGN: Prospective, randomized clinical pilot study. SETTING: Cardiothoracic Surgery Department in a university hospital. PATIENTS: Fourteen patients undergoing elective coronary artery bypass grafting were included. Seven patients underwent CPB using a standard, noncoated extracorporeal circuit, and seven patients had CPB using a heparin-coated extracorporeal circuit (Duraflo II). INTERVENTIONS: Blood samples were taken after induction of anesthesia, just before aortic crossclamping, and 0, 0.5, 1.5, 3, 6, 12, and 24 h after declamping. MEASUREMENTS AND RESULTS: CPB with a noncoated extracorporeal circuit induced a sharp increase in neutrophil-derived BPI, manifest directly after release of the aortic crossclamp, which was significantly attenuated using a heparin-coated system. Also, CPB induced a gradual increase of the acute-phase reactant LBP, which was identical in the noncoated and heparin-coated groups. Systemic release of sCD14 after crossclamp release was significantly higher in the noncoated group compared with the heparin-coated group, but did not rise above baseline levels. CONCLUSIONS: These data confirm that CPB-induced leukocyte activation is attenuated using a heparin-treated extracorporeal circuit and point to the possible role of LPS toxicity-modulating proteins in the systemic inflammatory response after bypass surgery.

Acute-Phase Proteins↗