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Biomedical subjects

Claudia Marsik

Publications and source records attributed to Claudia Marsik.

At least 19 recordsLinked to original sources
PubMed2006

Immunomodulatory effects of fosfomycin in an endotoxin model in human blood.

OBJECTIVES: Although a wide range of therapeutic strategies have been developed to improve the outcome of severe sepsis, a convincing reduction in mortality is lacking. Recently, increasing attention has been paid to immunomodulatory effects of antimicrobials. This study set out to explore the immunomodulatory effects of fosfomycin, a broad-spectrum antibiotic frequently used in septic patients, at the protein and molecular levels in vitro. METHODS: Whole blood from 11 healthy volunteers was incubated with 50 pg/mL endotoxin and 100 microg/mL fosfomycin or physiological sodium chloride for 4 h. Real-time RT-PCR was performed for various pro- and anti-inflammatory cytokines. Concentrations of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in the supernatant were measured using a commercially available ELISA. RESULTS: Incubation of human leucocytes with endotoxin increased messenger RNA (mRNA) levels of cytokines several thousand fold compared with baseline. The addition of fosfomycin significantly inhibited mRNA levels of pro-inflammatory cytokines such as IL-1-alpha, IL-6 and TNF-alpha after 2 h (P < 0.01), while no significant reduction was observed for the anti-inflammatory cytokines IL-4, IL-10 and IL-13 (P = 0.26). At the protein level, the concentrations of IL-6 and TNF-alpha increased approximately 3000- and 600-fold after 4 h of incubation with lipopolysaccharide as compared with baseline, respectively. Addition of fosfomycin significantly reduced cytokine levels by 56% and 73% for IL-6 and TNF-alpha, respectively. CONCLUSIONS: Fosfomycin extensively decreased mRNA levels and release of pro-inflammatory cytokines in human blood. The broad antimicrobial coverage of fosfomycin and its immunosuppressive effects could be clinically useful in patients with sepsis.

Anti-Bacterial Agents↗
PubMed2006

The C-reactive protein (+)1444C/T alteration modulates the inflammation and coagulation response in human endotoxemia.

BACKGROUND: C-reactive protein (CRP) plays a major role in the immune system and is an independent risk marker of cardiovascular disease. However, CRP's role in atherogenesis as innocent bystander, causative, or even protective agent, remains unresolved. The (+)1444C/T alteration in the CRP gene has been reported to determine basal CRP concentrations. We hypothesized that this alteration may also be associated with the degree of inflammatory response and coagulation activation in a well-standardized model of systemic inflammation. METHODS: We administered 2 ng/kg endotoxin [Escherichia coli bacterial lipopolysaccharide (LPS)] intravenously to stimulate inflammation in 91 healthy young Caucasian male paid volunteers (age range, 19-40 years). Participants were confined to bed rest and fasted for 8.5 h after LPS infusion. We collected blood samples before LPS infusion and at 0, 2, 6, and 24 h after LPS infusion to measure inflammation markers [interleukin 6 (IL6), tumor necrosis factor-alpha (TNFalpha)], temperature, and coagulation markers (prothrombin fragment F(1+2), D-dimer). We analyzed the CRP 3' untranslated variant with a mutagenic separated PCR assay. RESULTS: Basal concentrations of high-sensitivity CRP were approximately 40% lower in (+)1444CC alteration carriers than in T homozygous (TT) allele carriers (P = 0.04). In contrast, basal IL6 concentrations were 2-fold higher in wild-type C homozygous (CC) than in TT individuals (P = 0.01). In response to the LPS challenge, CC individuals had 4-fold higher peak TNFalpha concentrations (P <0.01), >2.5-fold higher peak IL6 concentrations (P <0.01), and increased temperature (P <0.01). Twenty-four hours after LPS challenge, prothrombin fragment F(1+2) concentrations were 75% higher and D-dimer concentrations 50% higher in CC than in TT individuals (P <0.05). CONCLUSIONS: Genetic factors regulating CRP concentrations also modulate the individual response to endotoxin-stimulated inflammation.

Adult↗
PubMed2006

The EGF A61G polymorphism is associated with disease-free period and survival in malignant melanoma.

An earlier study reported that a common polymorphism in the 5' untranslated region of the epidermal growth factor (EGF) gene is associated with increased risk for cutaneous malignant melanoma (MM) and Breslow thickness. Since then, several independent studies have reported conflicting results that have challenged this hypothesis. However, none of the previous studies examined survival as the primary outcome. We therefore sought to study the association between this polymorphism and survival. One hundred and thirty patients diagnosed with MM with a Breslow thickness of >1.5 mm were included in this study. In our collective, the G/G genotype represented a significant risk factor for both shorter disease-free period (hazard ratio of 2.246, 95% CI: 1.06-4.78, P=0.036) and overall MM-specific survival (hazard ratio of 3.8, 95% CI: 1.5-9.5, P=0.004) compared with the A/A genotype, while the heterozygous A/G genotype showed an intermediate risk. In the present study, we demonstrate for the first time that the EGF A61G polymorphism is associated with survival. Our data suggest that this polymorphism is a potential marker for disease severity that predicts earlier progression of MM.

5' Untranslated Regions↗
PubMed2006

Anti-cardiolipin antibodies and overall survival in a large cohort: preliminary report.

BACKGROUND: Anti-cardiolipin antibodies have been associated with both arterial and venous thrombosis, but their overall impact on all-cause or vascular mortality is unknown. In this study, we evaluated the influence of anti-cardiolipin antibodies on all-cause and vascular mortality. METHODS: All individuals who fulfilled the inclusion criteria (completeness of data, no admission from an intensive care unit, unique identification with name and date of birth) and whose anti-cardiolipin antibodies were measured between October 2002 and February 2004 were included in this study (n = 4756; 64% female; median age, 46 years). Death/survival and cause of death were obtained from the Austrian Death Registry. The median observation period was 1.5 years, and the study comprised 7189 person-years. RESULTS: During the study period, 184 patients (3.9%) died. There were no associations between either anti-cardiolipin IgM or IgG antibodies and both vascular death and noncancer mortality as outcome variables in a Cox regression analysis adjusted for age and sex. In contrast, the risk of cancer-related mortality was increased 2.6-fold. CONCLUSIONS: Anti-cardiolipin antibodies are associated with cancer mortality, likely as an epiphenomenon of malignancy, but they are not predictive of vascular mortality or noncancer mortality. Hence, although a clear association between anti-cardiolipin antibodies and (mostly nonfatal) vascular events has been described in the literature, our data indicate that this finding is not necessarily associated with an increase in vascular mortality.

Adult↗
PubMed2005

Clinical restenosis after coronary stent implantation is associated with the heme oxygenase-1 gene promoter polymorphism and the heme oxygenase-1 +99G/C variant.

BACKGROUND: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. METHODS: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. RESULTS: Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR)=1.9; 95% confidence interval (95% CI), 1.0-3.4; P=0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR=3.4; 95% CI, 1.2-9.1; P=0.017) in nonsmokers than in smokers (OR=2.0; 95% CI, 0.7-5.2; P=0.18). CONCLUSIONS: The long allele of the HO-1 gene promoter (>29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the >29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.

Aged↗
PubMed2005

Endotoxemia enhances expression of the signaling receptor (GP130) on protein and molecular level.

Interleukin 6 (IL-6) performs a prominent role during sepsis. To examine the molecular regulation of IL-6, IL-6 receptor, and signaling receptor gp130 during endotoxemia, nine healthy young volunteers received a bolus injection of lipopolysaccharide (LPS) on day 1 and saline on day 2 in a double blind, randomized, placebo-controlled trial. LPS enhanced IL-6 release 300-fold. IL-6 mRNA expression was not significantly altered in blood samples at any time after LPS infusion in vivo, while incubation of whole blood with 50 pg/ml LPS up-regulated IL-6 mRNA levels 8000- to 50,000-fold in vitro. LPS infusion increased synthesis of gp130 mRNA 5.5-fold compared to baseline at 4 h (P < 0.05), while no significant change was observed in the placebo period (P = 0.001 between groups). LPS increased the percentage of gp130 positive neutrophils gp130 700% over baseline at 8 h (P < 0.01 versus baseline and placebo). IL-6 receptor levels were not significantly altered by low-grade endotoxemia. In conclusion, endotoxemia up-regulates gp130 expression in vivo and in vitro. Quantification of IL-6 mRNA expression in circulating leukocytes is unlikely a suitable marker for monitoring of endotoxemia.

Adult↗
PubMed2005

Pharmacokinetics and pharmacodynamics of cefpirome in subcutaneous adipose tissue of septic patients.

The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broad-spectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (n = 11) and healthy controls (n = 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of Staphylococcus aureus and Pseudomonas aeruginosa. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 +/- 5.20 g . min/liter in healthy subjects and 6.90 +/- 2.56 g . min/liter in septic patients (P < 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (P < 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (T > MIC) in tissue were greater than 60% for pathogens for which the MIC was </=4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.

Adipose Tissue↗
PubMed2004

Effects of carbon monoxide inhalation during experimental endotoxemia in humans.

Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO may act as an antiinflammatory agent in human endotoxemia. The aim of this trial was to study the effects of CO inhalation on cytokine production during experimental human endotoxemia. The main study was a randomized, double-blinded, placebo-controlled, two-way cross-over trial in healthy volunteers. Each volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95% confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an approximately 200-fold increase). These LPS-induced changes were not influenced by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in rodents.

Administration, Inhalation↗
PubMed2004

The single nucleotide polymorphism Ser128Arg in the E-selectin gene is associated with enhanced coagulation during human endotoxemia.

The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is overrepresented in certain patient groups with atherosclerosis or restenosis. We hypothesized and tested whether it may affect cytokine-induced levels of soluble (s) E-selectin, or be associated with proinflammatory or procoagulant properties in a well-standardized inflammation model. Healthy male volunteers (n = 157) received a lipopolysaccharide (LPS) infusion and were genotyped for the S128R SNP, and outcome parameters were measured by enzyme immunoassays and real-time polymerase chain reaction (RT-PCR, Taqman). The S128R SNP had no pronounced effects on basal or inducible sE-selectin levels, or levels of tumor necrosis factor or interleukin-6. However, carriers of the S128R SNP had 20% higher monocyte counts at 24 hours after LPS infusion. Importantly, the S128R allele enhanced thrombin generation by 50% to 80%, as measured by prothrombin fragment F(1+2) (P < .01), and hence fibrin formation (D-dimer) 2-fold (P = .01 to P = .002). However, tissue factor (TF) mRNA levels were not affected. The S128R E-selectin genotype is associated with procoagulant effects in a human model of endotoxin-induced, TF-triggered coagulation. This could contribute to its linkage with various thrombotic cardiovascular disorders.

Amino Acid Substitution↗
PubMed2004

Simvastatin prevents vascular hyporeactivity during inflammation.

BACKGROUND: There is growing evidence that statins exert anti-inflammatory and antioxidative vascular actions that are independent of lipid lowering. We tested whether hyporeactivity to the endothelium-dependent vasodilator acetylcholine (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental inflammation could be prevented by simvastatin. METHODS AND RESULTS: In a randomized, placebo-controlled, parallel group study, forearm blood flow (FBF) responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo treatment, and during Escherichia coli endotoxin (lipopolysaccharide [LPS])-induced inflammation in 20 healthy volunteers. Additionally, markers of inflammation and neutrophil oxidative burst were assessed. Simvastatin and placebo had no effect on FBF or oxidative/inflammatory markers. LPS administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased responses to ACh by 48% (P<0.05) but did not decrease FBF responses to NTG. Simvastatin completely preserved responses to NE and to ACh. The LPS-induced increases in neutrophil oxidative burst and plasma tumor necrosis factor-alpha concentrations were mitigated by simvastatin (P<0.05 versus placebo). CONCLUSIONS: This study demonstrates potent vasoprotective properties of high-dose simvastatin during endotoxemia that may be useful for patients with acute systemic inflammation and associated vascular hyporeactivity.

Acetylcholine↗
PubMed2004

Effect of norepinephrine on cefpirome tissue concentrations in healthy subjects.

OBJECTIVES: To test whether norepinephrine (NOR) affects tissue microcirculation and impairs plasma-to-tissue equilibration of antimicrobial agents. MATERIALS AND METHODS: Eight healthy male volunteers were enrolled to an analyst-blinded, randomized, two-period two-sequence crossover study. A single intravenous dose of 2 g of cefpirome was administered simultaneously with starting a continuous infusion of NOR (0.16 microg/kg per min) or placebo (PL) over 180 min. The microdialysis technique was used for the assessment of unbound cefpirome concentrations in skeletal muscle tissue and subcutaneous adipose tissue. Free plasma concentrations were related to corresponding tissue concentrations. Haemodynamics were determined by the measurement of mean arterial blood pressure (MAP), heart rate and forearm blood flow (FBF). RESULTS: Area under the concentration-time-curve (AUC) values of cefpirome for interstitium and plasma were not significantly different between the PL and NOR groups (P > 0.47). Tissue penetration of cefpirome as described by the ratios of the AUCs from 0 to 180 min for tissue to the AUC values for plasma were 0.81 +/- 0.34 for the PL group and 0.80 +/- 0.26 for the NOR group (P > 0.05). Baseline values of MAP, heart rate and FBF were not significantly different between study days. MAP increased significantly following NOR administration from 73.3 +/- 3.5 mmHg at baseline to 94.0 +/- 5.2 mmHg during infusion (P = 0.017). NOR exerted no significant effects on FBF. CONCLUSIONS: We have shown that intravenous administration of NOR does not exert a significant effect on peripheral blood flow and tissue penetration of cefpirome in healthy men. This might be attributed to systemic regulatory mechanisms, which probably fully compensate for major changes in blood flow in peripheral tissues.

Adult↗
PubMed2004

Endotoxin down-modulates P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on neutrophils in humans.

P-selectin glycoprotein ligand-1 (PSGL-1, CD162), the counter-receptor for P-selectin and possibly E- and L-selectin, mediates rolling of leukocytes during inflammation and, thus, plays a pivotal role in hemostasis and inflammation. PSGL-1 is constitutively expressed on circulating leukocytes. Until recently, PSGL-1 has been considered not to be regulated upon cell activation. As modulation of PSGL-1 has only recently been reported for three proinflammatory substances, PSGL-1 regulation was examined during systemic inflammation in humans. Nine healthy human volunteers received a bolus of 2 ng/kg LPS i.v. Endotoxin infusion down-modulated PSGL-1 expression on neutrophils, with a maximum at 6-8 hr (-22%; P =0.001 vs. baseline and placebo), which correlated with peak neutrophilia. Similar PSGL-1 down-regulation was observed on monocytes. sPSGL-1 plasma levels increased trendwise after LPS infusion (+12% at 6 hr; P =0.10). In vitro LPS stimulation of whole blood significantly down-regulated PSGL-1 on neutrophils (-43%) and monocytes (-35%) as early as 2 hr ( P <0.05; n =5) in both EDTA and lepirudin anticoagulated samples. In summary, PSGL-1 is down-modulated on neutrophils and monocytes during endotoxemia in humans. PSGL-1 down-regulation could potentially facilitate the development of neutrophilia.

Analysis of Variance↗
PubMed2004

Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia.

OBJECTIVE: Clinical trials show that interleukin (IL)-6 represents a predictive marker in human sepsis. Furthermore, IL-6 has been proposed as a candidate mediator for endotoxin (lipopolysaccharide)-induced coagulation activation: In a primate model, an (alphaIL-6 antibody (alphaIL-6 Ab) almost abolished lipopolysaccharide-induced coagulation activation. Therefore, we wished to determine if an alphaIL-6 Ab (B-E8) may also attenuate lipopolysaccharide-induced activation of coagulation in humans. DESIGN: The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group). SETTING: University medical center. PATIENTS: Healthy volunteers. INTERVENTIONS: Healthy volunteers were randomized to receive either 80 mg of a monoclonal anti-IL-6 Ab (B-E8) or placebo intravenously before bolus infusion of 2 ng/kg lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: B-E8 effectively decreased IL-6 bioactivity as measured by a Bg-bioassay in vitro and concentrations of C reactive protein. However, B-E8 did not decrease lipopolysaccharide-induced tissue factor-messenger RNA transcription or plasma concentrations of downstream coagulation variables (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, and D-dimer concentrations). Similarly, tumor necrosis factor-alpha concentrations, fibrinolytic activity (plasmin-antiplasmin complexes), endothelial activation (soluble E-selectin), and IL-10 were unaffected. CONCLUSION: IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.

Adult↗
PubMed2004

Platelet function in mitochondriopathy with stroke and stroke-like episodes.

Stroke and stroke-like episodes are frequent complications in mitochondriopathy, particularly in MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes) which is a disorder of the mitochondrial oxidative metabolism in diverse cell types. To clarify a possible pathological aspect of stroke in these patients, we investigated platelet function before and after physical exercise. Ten patients with mitochondriopathy and stroke and ten healthy sex and age matched controls were investigated in an analyst blinded, prospective cross-sectional trial. Exercise decreased intraplatelet adenosine triphosphate (ATP) concentrations by -22% from baseline in patients with mitochondriopathy (p<0.01 between groups) while exercise increased ATP-levels by 28% healthy controls (p=0.01 vs baseline). Thrombin receptor activating peptide (TRAP) stimulated P-selectin expression increased up to 50% (p<0.05) in healthy subjects following exercise compared to 39% (p>0.05) in patients with mitochondriopathy. Exercise trendwise decreased platelet plug formation under shear stress by 24% in patients as measured by the platelet function analyzer PFA-100(R). Tromboelastography showed firm thrombus formation and delayed lysis in patients following exercise. In conclusion, this trial has shown that ATP depletion during and after exercise probably accounts for a defective oxidative metabolism in platelets of patients with mitochondriopathy and stroke. This might induce decreased platelet function in these patients but fails to explain the increased stroke rate. Therefore other mechanisms seem to be etiologically involved in the pathogenesis of stroke in patients with mitochondriopathy.

Adenosine Triphosphate↗
PubMed2004

The interleukin-6 G(-174)C promoter polymorphism does not determine plasma interleukin-6 concentrations in experimental endotoxemia in humans.

BACKGROUND: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays an essential role in the pathogenesis of acute and chronic infections. As the role of the IL-6 G(-174)C polymorphism in determining serum concentrations of IL-6 is controversial, we studied the genotype-specific IL-6 response in a well-standardized model of systemic inflammation. METHODS: A total of 76 healthy young males (age range, 19-35 years) received a single bolus of 2 ng/kg endotoxin [lipopolysaccharide (LPS)] intravenously. Plasma IL-6 was measured by enzyme immunoassay at 0, 2, 6, and 24 h after LPS infusion, and the IL-6 promoter genotype was analyzed by a mutagenic separated PCR assay. RESULTS: IL-6 increased 300-fold 2 h after LPS challenge and returned almost to normal within 24 h. Neither basal IL-6 nor the IL-6 response to LPS was significantly affected by the IL-6 promoter genotype. CONCLUSIONS: The IL-6 G(-174)C promoter polymorphism does not significantly influence basal concentrations of IL-6 or peak IL-6 in human endotoxemia.

Adult↗
PubMed2003

Inflammation-induced vasoconstrictor hyporeactivity is caused by oxidative stress.

OBJECTIVES: We sought to determine the role of oxidative stress in the development of vascular dysfunction in inflammation. BACKGROUND: Hyporeactivity to catecholamines and other vasoconstrictors is present in acute inflammation. Because oxidative stress plays a significant role in inflammation, impaired responsiveness may be overcome by anti-oxidants. METHODS: In randomized, double-blind, cross-over studies, forearm blood flow (FBF) responses to norepinephrine (NE), angiotensin II (ANG II), and vasopressin (VP) were assessed before and 4 h after induction of systemic inflammation by low doses of Escherichia coli endotoxin (lipopolysaccharide [LPS], 20 IU/kg intravenously) or after placebo in healthy volunteers. Furthermore, the effect of intra-arterial vitamin C (24 mg/min) or placebo on NE-induced or ANG II-induced vasoconstriction was studied after LPS. RESULTS: Administration of LPS caused systemic and forearm vasodilation, increased white blood cell count, elevated body temperature, and reduced vitamin C plasma concentrations. Lipopolysaccharide decreased the responses of FBF to NE by 59%, to ANG II by 25%, and to VP by 51% (n = 9, p < 0.05, all effects). Co-administration of vitamin C completely restored the response to NE and to ANG II, which was comparable to that observed under baseline conditions (n = 8). CONCLUSIONS: E. coli-endotoxemia reduces FBF responsiveness to vasoconstrictors. The hyporeactivity can be corrected by high doses of vitamin C, suggesting that oxidative stress may represent an important target for inflammation-induced impaired vascular function.

Adult↗
PubMed2003

Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation.

BACKGROUND: Tissue factor (TF), the main trigger of coagulation is important in the propagation of cardiovascular diseases. Based on an in vitro study, we hypothesised that enalapril may blunt the endotoxin-induced, TF-triggered coagulation in humans. METHODS: In a randomised, controlled trial, 30 healthy male volunteers received 2 ng/kg of lipopolysaccharide (LPS) after pre-treatment with placebo or enalapril for 5 days or with enalapril 2 h before LPS infusion. RESULTS: Infusion of LPS increased interleukin-6 levels 400 fold, and induced a 10-fold increase in prothrombin fragment, a fourfold increase in D-dimer, and a fivefold increase in plasmin-antiplasmin complexes. However, pre-treatment with enalapril did not blunt LPS-induced coagulation. CONCLUSIONS: Our trial provides evidence against a modulatory role of angiotensin converting enzyme in LPS-induced, TF-triggered coagulation.

Adult↗