atrial-natriuretic-factor and Sepsis

The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor (ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions of these hormones the heart contributes to the regulation of the cardiac preload and afterload. More recently, new functions for these hormones have been described including the modulation of the immune response. Plasma levels of BNP but not those of ANF, increase following an acute rejection episode of a cardiac allotransplant but return to levels pre-rejection with successful treatment. This observation constitutes the first observation leading to characterizing the interactions of BNP with the immune response. Several other pathologies with an inflammatory component are now known to be associated with an increase in the production of BNP. Such an increase is due to an increase in the transcriptional activity of the BNP gene induced by cytokines and related substances. In vitro investigations have shown that an increase in BNP directly modulates immunological activity. Inflammation and hemodynamic changes co-exist in several cardiovascular diseases and therefore it may be beneficial to measure circulating levels of both ANF and BNP as biomarkers of changes in intravascular volume and of changes in intravascular volume plus inflammation, respectively. Changes in plasma ANF, that are relatively larger than those of BNP, might be an indication of hemodynamic deterioration while important changes in circulating BNP could indicate a worsening of the inflammatory process.

Topics: Animals; Atrial Natriuretic Factor; Biomedical Research; Hemodynamics; Humans; Inflammation; Myocarditis; Myocytes, Cardiac; Natriuretic Peptide, Brain; Sepsis

As a continuation of "Postmortem Chemistry Update Part I," Part II deals with molecules linked to liver and cardiac functions, alcohol intake and alcohol misuse, myocardial ischemia, inflammation, sepsis, anaphylaxis, and hormonal disturbances. A very important array of new material concerning these situations had appeared in the forensic literature over the last two decades. Some molecules, such as procalcitonin and C-reactive protein, are currently researched in cases of suspected sepsis and inflammation, whereas many other analytes are not integrated into routine casework. As in part I, a literature review concerning a large panel of molecules of forensic interest is presented, as well as the results of our own observations, where possible.

Topics: Alcohol Drinking; Alcoholism; Anaphylaxis; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Forensic Pathology; Glucuronates; Heart Diseases; Heart Function Tests; Hormones; Humans; Inflammation; Liver; Liver Function Tests; Postmortem Changes; Protein Precursors; Sepsis; Sulfuric Acid Esters; Transferrin

Timely diagnosis of the different severities of septic inflammation is potentially lifesaving because therapies that have been shown to lower mortality should be initiated early. Sepsis and severe sepsis are accompanied by clinical and laboratory signs of systemic inflammation but patients with inflammation caused by noninfectious causes may present with similar signs and symptoms. It is important to identify markers for an early diagnosis of sepsis and organ dysfunction. This article presents currently interesting sepsis biomarkers. Other novel markers and their potential role are discussed.

Topics: Acute-Phase Proteins; Adrenomedullin; Animals; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Carrier Proteins; Complement C3a; Cytokines; Endotoxins; HLA-DR Antigens; Humans; Membrane Glycoproteins; Natriuretic Peptide, Brain; Neoplasm Proteins; Neopterin; Peptides; Protein C; Protein Precursors; Proteoglycans; Receptors, Immunologic; Sensitivity and Specificity; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

Biochemical markers are available to detect cardiac involvement in many pediatric disease states and should be considered.. Analyses of three markers are readily available in clinical laboratories for improved diagnosis.. Increased workload of the heart has been associated with the release of biochemical markers (natriuretic peptides and cardiac enzymes) that indicate that a new genetic program has been activated and maladaptation is occurring in the atria, ventricles, or both. This review summarizes those that have been identified in fetal and pediatric practice. The expression of such markers is traced from early embryonic development to fetal life, to the neonate, to childhood, and then to adult life.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biomarkers; Child; Graft Rejection; Heart Diseases; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Renal Insufficiency; Sepsis; Troponin T

Endothelial glycocalyx (EG) shedding is associated with septic shock and described following intravenous (IV) fluid administration. To investigate the possible impact of IV fluids on the pathobiology of septic shock we investigated associations between biomarkers of EG shedding and endothelial cell activation, and relationships with IV fluid volume. Serum samples were obtained on admission (T0) and at 24 h (T24) in patients undergoing haemodynamic resuscitation for suspected septic shock in the emergency department. Biomarkers of EG shedding-Syndecan-1 (Syn-1), Syndecan-4 (Syn-4), Hyaluronan, endothelial activation-Endothelin-1 (ET-1), Angiopoeitin-2 (Ang-2), Vascular Endothelial Growth Factor Receptor-1(VEGF-1) and leucocyte activation/inflammation-Resistin, Neutrophil Gelatinase Associated Lipocalin (NGAL) and a marker of cardiac stretch-Pro-Atrial Natriuretic Peptide (Pro-ANP) were compared to the total IV fluid volume administered using Tobit regression. Data on 86 patients (52 male) with a mean age of 60 (SD 18) years were included. The mean fluid volume administered to T24 was 4038 ml (SD 2507 ml). No significant association between fluid volume and Pro-ANP or any of the biomarkers were observed. Syn-1 and Syn-4 were significantly correlated with each other (Spearman Rho 0.43, p < 0.001) but not with Hyaluronan. Syn-1 and Syn-4 both correlated with VEGFR-1 (Rho 0.56 and 0.57 respectively, p < 0.001) whereas Hyaluronan correlated with ET-1 (Rho 0.43, p < 0.001) and Ang-2 (Rho 0.43, p < 0.001). There was no correlation between Pro-ANP and any of the EG biomarkers. Distinct patterns of association between biomarkers of EG shedding and endothelial cell activation were observed among patients undergoing resuscitation for sepsis. No relationship between IV fluid volume and Pro-ANP or any of the other biomarkers was observed.

Topics: Atrial Natriuretic Factor; Biomarkers; Emergency Service, Hospital; Glycocalyx; Humans; Hyaluronic Acid; Male; Middle Aged; Sepsis; Shock, Septic; Vascular Endothelial Growth Factor A

Myocardial injury is a common complication of sepsis. MicroRNA (miRNA) miR-214-3p is protective against myocardial injury caused by sepsis, but its mechanism in lipopolysaccharide (LPS)- induced cardiomyocyte injury is still unclear. An AC16 cell injury model was induced by LPS treatment. Cell Counting Kit-8 and flow cytometry assay showed decreased cell viability and increased apoptosis in LPS-treated AC16 cells. The levels of caspase- 3, Bax, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), myosin 6 (Myh6), myosin 7 (Myh7), reactive oxygen species (ROS), and malondialdehyde (MDA) were increased in LPS-treated AC16 cells, but the levels of Bcl-2 and superoxide dismutase (SOD) were decreased. MiR-214-3p was down-regulated and cathepsin B (CTSB) was upregulated in LPS-treated AC16 cells. At the same time, miR-214-3p could target CTSB and reduce its expression. We also found that a miR-214-3p mimic or CTSB silencing could significantly reduce LPSinduced apoptosis, decrease ROS, MDA, caspase-3, and Bax and increase SOD and Bcl-2. CTSB silencing could significantly reduce ANP, BNP, Myh6, and Myh7 in LPS-treated AC16 cells. The effects of CTSB silencing were reversed by a miR-214-3p inhibitor. In summary, miR-214-3p could inhibit LPSinduced myocardial injury by targeting CTSB, which provides a new idea for myocardial damage caused by sepsis.

Topics: Atrial Natriuretic Factor; bcl-2-Associated X Protein; Cathepsin B; Humans; Lipopolysaccharides; MicroRNAs; Myocytes, Cardiac; Reactive Oxygen Species; Sepsis; Superoxide Dismutase

The significance of the validated biomarkers of sepsis Mid-regional pro-atrial natriuretic peptide (MR-proANP) and copeptin have not been tested in a burn injury setting.. 42 consecutive patients were included in a prospective observational study. Daily blood specimens collected over the initial 20 days of treatment were quantitatively analysed by immunoluminometric sandwich assay (Kryptor, BRAHMS, Berlin, Germany) for MR-proANP, copeptin and procalcitonin (PCT).. In patients with absence of sepsis, copeptin levels initially increased post-burn injury and thereafter rapidly declined. In contrast, MR-proANP was only slightly elevated within the first few days. MR-proANP [199.8 (115.6; 399.5) vs 160.1 (93.7; 280.6), P < .007] and PCT [1.12 (0.32; 2.22) vs 0.32 (0.16; 0.53), P < .001] levels were significantly higher on days of sepsis. Copeptin, however, showed no significant differences [20.7 (11.8; 42.2) vs 16.8 (11.0; 30.6), P = .11]. Both, MR-proANP and PCT level increases were noted upon the first day of sepsis.. Burn injury itself maybe associated with copeptin and to a lesser degree MR-proANP level increases. Subsequent increases in MR-proANP may be considered diagnostic for sepsis but demonstrated no advantages over PCT. The role of copeptin remains inappropriate for diagnosing sepsis after burn injury (ClinicalTrials.gov number, NCT01055587).

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Burns; Female; Glycopeptides; Humans; Male; Middle Aged; Prospective Studies; Sepsis

Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation.. We used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate.. Consistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113-341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45-79] ng/ml), as well as in a second cohort of sepsis patients (283 [155-584] ng/ml) at emergency department presentation) compared to controls (177 [144-262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment.. Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

Topics: Administration, Intravenous; Adult; Aged; Angiopoietin-2; Atrial Natriuretic Factor; Biomarkers; Endothelium; Female; Fluid Therapy; Glycocalyx; Heparitin Sulfate; Humans; Male; Mass Spectrometry; Middle Aged; Natriuretic Peptide, Brain; Resuscitation; Sepsis; Syndecan-1; Thrombomodulin; Tissue Plasminogen Activator; Vascular Endothelial Growth Factor Receptor-1

The aim of this paper is to investigate whether urosepsis is related to irrigation pressure of ureteroscopy (URS) and evaluate the prognostic value of adrenomedullin (ADM) and atrial and brain natriuretic peptides (ANP and BNP) in URS-induced uroseptic patients. From July 2008 to October 2013, we enrolled 332 patients with untreated unilateral ureteral obstruction (UUO). The UUO group included three subgroups of, respectively, 118, 132, and 82 patients who underwent URS under intermittent stable irrigation pressure of, respectively, 80, 120, and 160 mmHg. The plasma concentrations of ADM, ANP, and BNP were measured in all subjects. URS was performed for all UUO patients; the values of the three peptides were measured again after URS. Irrigation pressure and stone size were independent risk factors of urosepsis. After URS, the plasma concentrations of ADM, ANP, and BNP were significantly higher in uroseptic patients. Moreover, the concentrations were significantly higher depending on the disease severity. Plasma concentrations of the three peptides were correlated with plasma ET concentration in the uroseptic patients. The areas under receiver operating characteristic (ROC) curve of ADM, ANP, and BNP for predicting urosepsis were 0.811, 0.728, and 0.764, respectively. In conclusion, ADM, along with ANP and BNP, is valuable for prognosis in urosepsis secondary to URS which is associated with irrigation pressure.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sepsis; Ureteroscopy; Urinary Tract Infections; Young Adult

Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were significantly lower, while A-FaBP and mrProANP were higher in septic patients compared to the control groups. Each biomarker was associated with hospital morbidity and length of stay. These results suggest that these biomarkers merit further prospective study for the early identification of children with sepsis.

Topics: Adipocytes; Adolescent; Adult; Atrial Natriuretic Factor; Biological Assay; Biomarkers; Case-Control Studies; Child; Child, Preschool; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Matrix Metalloproteinase 9; Nervous System Diseases; Prognosis; Prospective Studies; Sepsis; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-1

In the critical care setting, increasing levels of midregional proadrenomedullin (MRproADM), midregional proatrial natriuretic peptide (MRproANP), procalcitonin (PCT), copeptin, and proendothelin-1 (proET-1) have been shown to be correlated with increasing severity of sepsis. The objective of this study was to investigate the utility of sepsis biomarkers in an Emergency Department (ED) population.. Through a prospective, observational pilot study, we investigated the utility of MRproADM, MRproANP, PCT, copeptin, and proET-1 in predicting a diagnosis of early sepsis in patients presenting to the ED for suspected infection. Data were analyzed using nonparametric Mann-Whitney U-tests, χ²-tests, and receiver operating characteristic curves.. Of the 66 patients enrolled in this study, 37 (56.1%) were men, with a median age of 58 years [interquartile range (IQR) 39-69 years], and 19 (28.8%) had a final diagnosis of early sepsis. A higher percentage of sepsis patients compared with no-sepsis patients met systemic inflammatory response syndrome (SIRS) criteria at initial presentation (85.7 vs. 41.3%; P<0.0001) and were admitted to the hospital (84.2 vs. 55.6%; P=0.02). PCT was higher in sepsis patients [median 0.32 ng/ml (IQR 0.19-1.17) vs. 0.18 ng/ml (IQR 0.07-0.54); P=0.04]. There were no differences between groups for MRproADM, MRproANP, copeptin, or proET-1 (P≥0.53). The C-statistic was maximized with the combination of SIRS criteria and PCT levels (0.92±0.05), which was better than PCT alone (0.67±0.08; P=0.005) or SIRS alone (0.75±0.07; P=0.04).. In this pilot study, we found that the combination of SIRS criteria and PCT levels is useful for the early detection of sepsis in ED patients with suspected infection. Larger studies investigating use of PCT are necessary.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Endothelin-1; Female; Glycopeptides; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Protein Precursors; Sepsis

To evaluate the clinical value and specificity of atrial natriuretic peptide (ANP) in early diagnosis of sepsis.. A prospective study was performed. Data of patients with sepsis were consecutively collected from September 2007 to December 2012 according to the international criteria for the diagnosis of sepsis, and that of 114 patients admitted to intensive care unit (ICU) and the cadre health care ward were divided into three groups: systemic inflammatory response syndrome (SIRS) group (n=37), sepsis group (n=41) and severe sepsis group (including severe sepsis and septic shock, n=36). Venous blood of each patient was drawn instantly when admitted to ICU. The concentration of plasma ANP in each group was determined on the 1st day using a new type of sandwich immunofluorescence assay, and other biomarkers, such as procalcitonin (PCT, detected with double antibody immunochemi luminometry), blood lactic acid (detected with electrode meter), and C-reactive protein (CRP, detected with immunonephelometric analysis), and the acute physiology and chronic health evaluation II (APACHEII) score was recorded. APACHEII score and biomarkers were compared among three groups. The risk factor for severity was confirmed with stepwise regression, and the value of each index in early diagnosis of sepsis was analyzed with receiver operating characteristic (ROC) curve.. The plasma concentration of ANP exhibited a gradual increase with the aggravation of the disease, and the median ANP value was found to be highest in the severe sepsis group compared with SIRS group and sepsis group [μg/L: 0.26 (0.22) vs. 0.19 (0.05), 0.21 (0.08), P<0.01 and P<0.05]. The regression equation was established at y=0.69 + 0.66APACHEIIscore + 1.285 ANP value, with group as independent variable, and APACHEII score, ANP, PCT, CRP and blood lactic acid value as dependent variables. It could be concluded that APACHEII score and ANP value were correlated with severity of sepsis, and accordingly they were regarded as the independent predictors of severity of sepsis. It was found through the ROC curve analysis of ANP in the sepsis patients, that the area under the ROC curve for ANP [0.805, P=0.000, 95% confidence interval (95%CI) 0.726-0.883, sensitivity 75.8%, specificity 78.4%] was similar with the area under the APACHEII score (0.820, P=0.000, 95%CI 0.742-0.897, sensitivity 68.4%, specificity 78.4%), and it was apparently higher than AUCs of PCT (0.716, P=0.000, 95%CI 0.622-0.810, sensitivity 67.1%, specificity 62.2%), CRP (0.569, P=0.236, 95%CI 0.463-0.675, sensitivity 76.3%, specificity 41.5%), or blood lactic acid (0.566, P=0.254, 95%CI 0.453-0.679, sensitivity 75.0%, specificity 48.6%).. Plasma ANP concentration is clinically valuable in early diagnosis and severity assessment of sepsis, and it is more specific and sensitive than biomarkers PCT and CRP.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Early Diagnosis; Female; Humans; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

We investigated the expression and secretion of the natriuretic peptides (NPs) ANF and BNP in lipopolysaccharide (LPS)-induced sepsis and its association with cytokines and other biologically active substances. LPS treatment increased plasma levels of ANF and BNP. The latter increase was larger than the increase in plasma ANF. LPS also increased cardiac content and gene expression of BNP but not of ANF. LPS treatment significantly increased gene expression cytokines, chemokines and proteases, which significantly correlated with BNP gene expression. SB203580, a p38 MAP kinase inhibitor, inhibited the elevation of BNP in plasma. The present work suggests that during inflammation, BNP gene expression and secretion is uniquely related to changes in gene expression in the absence of hemodynamic changes and hence differentiates ANF and BNP as biomarkers of cardiac disease.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cytokines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation; Imidazoles; Inflammation; Lipopolysaccharides; Myocardium; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Pyridines; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction

To establish the prognostic and discriminative value of the pro-atrial natriuretic peptide (pro-ANP) level in patients with severe sepsis or septic shock.. An observational and prospective study was conducted on 50 critically ill patients with severe sepsis or septic shock. Measurements of the level of procalcitonin (PCT) and mid-regional pro-ANP were determined in the serum of patients with commercially available immunoluminometric tests.. The median pro-ANP level was significantly higher in non-survivors than in survivors (P < 0.05) on all consecutive days. No significant differences in the pro-ANP levels were observed in patients with severe sepsis and septic shock. There was a strong correlation between the PCT and pro-ANP levels on admission in non-survivors and in septic shock patients (r = 0.56, P = 0.007 and r = 0.43, P = 0.02, respectively).. pro-ANP evaluated in severe sepsis and septic shock patients is a valuable prognostic biomarker, but, in contrast to PCT, which is routinely used as a diagnostic marker of severe sepsis and septic shock, it does not possess diagnostic and discriminative value.

Topics: Adolescent; Adult; Aged, 80 and over; APACHE; Atrial Natriuretic Factor; Bacteria; Biomarkers; Female; Fungi; Humans; Intensive Care Units; Male; Middle Aged; Poland; Predictive Value of Tests; Prognosis; Prospective Studies; Sepsis; Shock, Septic; Young Adult

To establish reference values in cord blood of the following new sepsis markers: pro-adrenomedullin (MR-proADM), pro-endothelin (CT-proET-1), and pro-atrial natriuretic peptide (MR-proANP).. MR-proADM, CT-proET-1, MR-proANP, and procalcitonin (PCT) were measured in cord blood of newborn infants by Time Resolved Amplified Cryptate Emission (TRACE) technology. The inclusion criteria in the control group (n=194) was the absence of any clinical sign or risk factor of sepsis. A group of 73 newborn infants presenting with risk factors of sepsis at delivery was also studied.. The median values (reference interval) of CT-proET-1, MR-pro-ADM, and MR-proANP measured in cord blood plasma were 72 pmol/L (39-115), 0.84 nmol/L (0.5-1.38), and 163 pmol/L (76-389), respectively. The PCT reference interval was not significantly different from that previously described in cord blood serum.. The reference intervals established will serve as a starting point for further clinical investigations aimed to elucidate the potential prognostic/diagnostic value of these markers in neonatal sepsis management.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endothelin-1; Female; Fetal Blood; Fetus; Humans; Infant; Infant, Newborn; Photoelectron Spectroscopy; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Protein Precursors; Reference Values; Sepsis

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Medical Services; Female; France; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Pyelonephritis; Sepsis

Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores.. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay.. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores.. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

Topics: Adolescent; Adrenomedullin; Adult; Aged; APACHE; Atrial Natriuretic Factor; C-Reactive Protein; Female; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic

This study aimed to investigate the correlation of midregional pro-atrial natriuretic peptide (MR-proANP) with severity of septic status in patients with ventilator-associated pneumonia (VAP) and the usefulness of MR-proANP for mortality prediction in VAP.. Prospective observational cohort study.. University Hospital.. Seventy-one patients consecutively admitted to ICU who developed VAP. Patients were followed for 28 days after diagnosis, when they were considered survivors. There were no interventions.. MR-proANP levels increased from sepsis to severe sepsis and septic shock on D0 and D4 of VAP (0.002 and 0.02 respectively). Median MR-proANP levels on day 0 and day 4 (pmol/L [interquartile range]) were 149.0 (79.8-480.0) and 249.0 (93.6-571.0) in septic patients, 438.5 (229.3-762.0) and 407.5 (197.8-738.0) in severe sepsis, 519.5 (369.5-1282.3) and 632.0 (476.0-1047.5) in septic shock. On day 0 and day 4, MR-proANP levels were significantly higher in non-survivors (525.0 [324.0-957.8] and 679.5 [435.0-879.5], respectively) than in survivors (235.0 [102.0-535.0] and 254.0 [110.0-571.0], respectively; P = 0.004). Univariate logistic regression model for mortality included age, gender, APACHE II score, creatinine, logarithmic transformed MR-proANP (LnMR-proANP). Mortality was directly related to LnMR-proANP on D0 and D4, with odds ratios (OR) of 2.06 (95% CI 1.21-3.51) and 2.63 (1.33-5.23), respectively. In multivariate logistic regression, only LnMR-proANP D0 with OR = 2.35 (1.05-5.26) and LnMR-proANP D4 with OR = 3.76 (1.39-10.18) remained significant.. Our data demonstrated that MR-proANP levels increase progressively with the severity of sepsis and are independent predictors of mortality in VAP.

Topics: Atrial Natriuretic Factor; Biomarkers; Brazil; Female; Humans; Logistic Models; Male; Middle Aged; Pneumonia, Ventilator-Associated; Predictive Value of Tests; Prognosis; Prospective Studies; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Survival Rate

Sepsis causes changes in vascular resistance and hypovolemia. Previous studies have demonstrated that the spleen regulates blood volume via atrial natiuretic peptide (ANP). We hypothesized that LPS alters extrasplenic responses to ANP via endothelial-dependent mechanisms and studied the role of NO and endothelin 1 (ET-1). Isolated extrasplenic arteries and veins (vessels in mesentery adjoining spleen) were obtained from male Wistar rats weighing 200 to 280 g (n = 102) and mounted on a pressure myograph to determine intraluminal diameter for 4 h. Isolated vessels constricted in response to the half-maximum response of ANP (veins, 30% +/- 1.7%; arteries, 34.5 +/- 1.7%; P < 0.05), and this was abolished by the NO donor S-nitroso-N-acetylpenicillamine (SNAP 75 microM). Arteries and veins incubated with LPS (50 microg mL(-1) for 4 h) were unresponsive to ANP, and constriction was not restored by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 100 microM). However, venular constriction returned in the presence of the ET-1 antagonist Bosentan, increasing from -1.5 +/- 1.2 (10 min) to -10 +/- 2.5% (4 h) with LPS + Bosentan (3 x 10(-6) M) compared with -2.3 +/- 1.2 and 0% with LPS alone. In conclusion, LPS abolished endothelial-dependent extrasplenic venular constriction to ANP partially due to increased ET-1, whereas NO seemed to modulate vascular responses to ANP.

Topics: Animals; Antihypertensive Agents; Arteries; Atrial Natriuretic Factor; Blood Volume; Bosentan; Endothelin-1; Enzyme Inhibitors; Hypovolemia; Lipopolysaccharides; Male; Mesentery; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Penicillamine; Rats; Rats, Wistar; Sepsis; Spleen; Sulfonamides; Vascular Resistance; Vasoconstriction; Veins

Sepsis intervention studies need better patient stratification methods, and one way to realize this is the introduction of stable biomarkers. A set of recently developed novel biomarkers, based upon precursor-fragments of short-lived hormones, was previously shown to be increased during sepsis. However, it is not known whether these biomarkers are influenced by sepsis intervention strategies. Therefore we investigated the markers in a model of human endotoxemia intervened by increasing doses of prednisolone.. Prospective, open-label study in a specialized clinical research unit of a university hospital.. Thirty-two healthy male volunteers.. Subjects received prednisolone orally at doses of 0, 3, 10 or 30 mg (n=8 per group) at 2 h before intravenous injection of Escherichia coli lipopolysaccharide (LPS) (4 ng/kg). Blood samples were drawn during 24 h after LPS injection.. LPS injection caused an increase in levels of midregional pro-adrenomedullin (MR-proADM), midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine-vasopressin (CT-proAVP) and procalcitonin (PCT). Prednisolone caused a dose dependent inhibition of MR-proADM, MR-proANP and CT-proAVP levels.. These results show that a set of novel, highly stable sepsis biomarkers was increased during human endotoxemia and was dose-dependently inhibited by corticosteroid pre-treatment.

Topics: Administration, Oral; Adrenomedullin; Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Dose-Response Relationship, Drug; Endotoxemia; Humans; Inflammation Mediators; Injections, Intravenous; Lipopolysaccharides; Male; Peptide Hormones; Prednisolone; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

Elevated plasma A-type natriuretic peptide (ANP) levels in sepsis cause fluid transfer into extravascular spaces. We investigated the changes in ANP concentrations and natriuretic peptide receptor (NPR) expression induced by thiorphan, a neutral endopeptidase (NEP) inhibitor, in a rat model of sepsis.. Fifteen male rats were divided into three groups: a control group (n = 5), a lipopolysaccharide (LPS) group (n = 5), and an LPS-thiorphan group (n = 5). We measured ANP concentrations in the plasma and lung, and NPR mRNA expression in the lung 4 h after administering LPS, and compared the values with those in the control group.. Plasma and lung ANP levels in the LPS group were significantly higher than those in the control group (P < 0.05), but were significantly decreased by thiorphan administration (P < 0.05). NPR-A mRNA levels did not differ significantly among the groups. NPR-C mRNA levels in the LPS-thiorphan group were significantly higher than those in the other groups (P < 0.05).. Elevated ANP levels were decreased by thiorphan administration, which increased NPR-C mRNA levels in the lung. Thus, thiorphan might be effective for reducing elevated ANP levels in sepsis.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Lung; Male; Protease Inhibitors; Rats; Receptors, Atrial Natriuretic Factor; Sepsis; Thiorphan

Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores.. Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay.. On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score.. Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sepsis; Shock, Septic

Increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been identified as predictors of cardiac dysfunction and prognosis in congestive heart failure and ischemic heart disease. In severe sepsis patients, however, no information is available yet about the prognostic value of natriuretic peptides. Therefore, the aim of the present study was to determine the role of the N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C [drotrecogin alfa (activated)] on plasma levels of natriuretic peptides in severe sepsis was evaluated.. Fifty-seven patients with severe sepsis were included. Levels of NT-proANP and NT-proBNP were measured on the second day of sepsis by ELISA. Septic patients with NT-proBNP levels >1400 pmol/L were 3.9 times more likely (relative risk [RR], 3.9; 95% CI, 1.6 to 9.7) to die from sepsis than patients with lower NT-proBNP values (P<0.01). NT-proANP levels, however, were not predictive of survival in our patient population. A highly significant correlation was found between troponin I levels and plasma concentrations of NT-proBNP in septic patients (r=0.68, P<0.0001). In addition, troponin I significantly accounted for the variation in NT-proBNP levels (P<0.0001), suggesting an important role for NT-proBNP in the context of cardiac injury and dysfunction in septic patients. Twenty-three septic patients who received treatment with drotrecogin alfa (activated) presented with significantly lower concentrations of NT-proANP, NT-proBNP, and troponin I compared with patients not receiving drotrecogin alfa (activated).. NT-proBNP may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

Topics: Adult; Aged; APACHE; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein C; Recombinant Proteins; Sepsis; Troponin I; Ventricular Function, Left

The family of natriuretic peptides comprises several structurally related 22-53-amino acid peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are vasoactive peptides with vasodilator and diuretic properties and play an important role in cardiovascular homeostasis. The salutary cardiovascular effects of natriuretic peptides suggest that ANP and BNP may have a pathophysiological significance in the cardiac dysfunction of septic patients. We determined plasma levels of the stable N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) as well as troponin I (TNI) as a marker of myocardial cell injury by ELISA methods in 19 septic patients and 19 healthy controls at day one of severe sepsis. Left ventricular ejection fraction (LVEF) was determined on day 1 of severe sepsis by echocardiography. Significantly higher concentrations of NT-proANP were measured in non-survivors (mean = 13415 pmol/l +/- SEM = 4295) and survivors (mean = 7386 pmol/l +/- SEM = 1807) as compared to controls (mean = 1404 pmol/l +/- SEM = 181; p<0.001). Levels of NT-proBNP were also significantly higher in non-survivors (mean = 3439 pmol/l +/- SEM = 1246; p<0.05) and survivors (mean = 1009 pmol/l +/- SEM = 263; p<0.001) as compared to controls (mean = 200 pmol/l +/- SEM = 24) and correlated well with an increase in TNI-levels (r = 0.71; p<0.001). NT-proANP and NT-proBNP may serve as useful laboratory markers to indicate myocardial dysfunction and may help to differentiate between survivors and non-survivors of severe sepsis.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Sepsis; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left

N-terminal prohormone of atrial natriuretic peptide ((proANP(1-98)) has been extensively analyzed in patients with chronic renal failure. It has been found to be closely related to the renal function and to interdialytic hydration status. The clinical relevance of proANP(1-98) and cystatin C, a novel marker of glomerular filtration, has not been investigated in the subgroup of critically ill septic patients with no history of chronic renal impairment.. We measured plasma level ofproANP(1-98) and cystatin C in 29 critically ill septic patients on admittance to the surgical intensive care unit and correlated it with the occurrence of acute renal failure.. The proANP(1-98) plasma level was significantly higher in the group of patients who developed renal failure (12,722 +/- 12,421 vs. 2,801+/- 2,023 fmol/ml, p < 0.05). Multiple regression analysis shows that proANP(1-98) on the first day in the intensive care unit has a superior predictive value for the occurrence of renal failure to diuresis, calculated creatinine clearance or cystatin C (r = 0.42, p < 0.039). proANP(1-98) is also higher in non-survivors (9,303.8 +/- 11,053 vs. 2,448.5 +/- 1,803 fmol/ml, p < 0.018).. proANP(1-98) is possibly a better predictor of acute renal failure to calculated creatinine clearance or diuresis among critically ill septic patients. Cystatin C was not correlated with occurrence of acute renal failure in this subgroup of patients.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Critical Illness; Cystatin C; Cystatins; Female; Humans; Male; Middle Aged; Peptide Fragments; Peritonitis; Predictive Value of Tests; Prospective Studies; Sepsis

Atrial natriuretic peptide is regarded as an important regulator of pulmonary vasomotor tone and permeability. This study investigated the role of atrial natriuretic peptide in sepsis-associated pulmonary pathophysiology.. Prospective experimental investigation.. Laboratory at a university hospital.. Twelve awake, chronically instrumented sheep.. The sheep were instrumented with lung lymph fistulas and received a continuous infusion with live Pseudomonas aeruginosa for 48 hrs. After 40 hrs, the atrial natriuretic peptide-receptor antagonist HS-142-1 was continuously infused in the HS-124-1 group (3 mg/kg/hr, n = 6) for 8 hrs, whereas the control group received the carrier (n = 6).. Lung lymph flow was markedly elevated in response to sepsis after 40 hrs in both groups. Atrial natriuretic peptide-receptor blockade further increased lymph flows by 41 +/- 17% (41 hrs) up to 64 +/- 20% (44 hrs, p < .05) in the presence of normal permeability to protein. Although mean pulmonary artery pressure increased (p < .05 vs. 40 hrs), capillary pressure remained unaffected. Despite identical fluid balances in both groups, cardiovascular filling variables significantly increased in the HS-142-1 group. This was associated with increasing cardiac index and mean arterial pressure (p < .05 vs. 40 hrs). In the control group, all variables remained constant between 41 and 48 hrs.. Blockade of atrial natriuretic peptide receptors increases pulmonary transvascular fluid flux independent of changes in permeability to protein in chronic ovine sepsis. Atrial natriuretic peptide may therefore play a protective role for the alveolar-capillary barrier during sepsis.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Female; Lung; Lymphatic System; Male; Permeability; Pseudomonas Infections; Pulmonary Circulation; Pulmonary Edema; Receptors, Atrial Natriuretic Factor; Reference Values; Risk Factors; Sensitivity and Specificity; Sepsis; Sheep, Domestic

The mechanisms underlying myocardial dysfunction in sepsis remain poorly understood. The theoretical benefits of nitric oxide synthase (NOS) inhibition in reversing the haemodynamic changes that characterise septic shock have not been supported by clinical trials, some of which have demonstrated detrimental myocardial effects. We have therefore assessed the effects of endotoxaemia on NOS enzyme expression as well as a number of functional responses of myocardial tissue from rats. Atrial tissue expressed high levels of mRNA for inducible (i) NOS and released increased levels of nitrite after animals were treated with endotoxin. In parallel, the inotropic response stimulated by isoprenaline was reduced in atria from endotoxin-treated animals, an effect that was reversed when endogenous release of NO was maximised. Our results suggest that myocardial contractility is maintained by NO production and that inhibitors may compromise cardiac output; this may explain the deleterious effects of NOS inhibition on cardiac function in clinical trials.

Topics: Animals; Atrial Natriuretic Factor; Cell Death; Electric Stimulation; Enzyme Inhibitors; Heart; Heart Atria; L-Lactate Dehydrogenase; Lipopolysaccharides; Male; Myocardial Contraction; Myocardium; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; omega-N-Methylarginine; Organ Culture Techniques; Rats; Salmonella enteritidis; Sepsis; Shock, Septic

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.

Topics: Acute Disease; Anesthesia; Angiotensin II; Animals; Atrial Natriuretic Factor; Endothelin-1; Escherichia coli Infections; Female; Femoral Vein; Hemorrhage; Hypovolemia; Male; Neuropeptides; Portal Vein; Sepsis; Splanchnic Circulation; Swine; Vasoconstrictor Agents

To test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis.. Prospective, randomized, controlled animal trial.. Research laboratory at a large university medical center.. Chronically instrumented Merino breed ewes (n = 18).. Continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (25 mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium chloride 0.9%.. The sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p < .05), and an increased cardiac index (p < .05) by 24 hrs. The sheep retained fluid, with creatinine clearance decreasing in the presence of chronically increased atrial natriuretic peptide. After the administration of N omega-nitro-L-arginine methyl ester, systemic vascular resistance index and cardiac index returned to baseline values, fluid balance normalized, and glomerular filtration rate increased (p < .05), while the control animals continued to retain fluid and their creatinine clearance continued to decrease. The concentrations of atrial natriuretic peptide did not differ significantly between groups after N omega-nitro-L-arginine methyl ester administration.. In this ovine model of experimental hyperdynamic sepsis, renal excretory function decreases in the presence of chronically increased concentrations of atrial natriuretic peptide. Administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.

Topics: Animals; Arginine; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Endotoxins; Female; Glomerular Filtration Rate; Hemodynamics; Kidney; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Sepsis; Sheep; Vascular Resistance

Continuous pump-driven veno-venous hemofiltration (CVVH) has become an established method for treatment of acute renal failure (ARF). Since severe disturbances of (micro-) circulation are intimately involved in the bad outcome of these patients, the profile of endocrinological regulators of circulation was prospectively and serially measured in patients undergoing pump-driven CVVH (n = 15). 15 patients with similar APACHE II score, but without ARF and without CVVH were also studied. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured before start of CVVH (= "baseline") (in the non-CVVH patients: admission to intensive care unit) and during the next 5 days. Various hemodynamic parameters were additionally monitored. MAP, HR, PAP, CI, and right ventricular hemodynamics (RVEF, RVEDV, RVESV) remained almost unchanged in the CVVH patients and were without differences to the non-CVVH group within the entire investigation period. PCWP and RAP were higher in the CVVH patients already at baseline (RAP, 17.8 +/- 4.0 mmHg; PCWP, 22.1 +/- 4.5 mmHg) (p < .02) and remained elevated in the further course of the investigation. Renin plasma level was higher already at baseline in the CVVH patients (907 +/- 184 pg/ml) (p < .05) and further increased during CVVH (to 1453 +/- 186 pg/mL). Vasopressin increased only in the CVVH group (from 3.80 +/- .66 to 11.85 +/- 1.05 pg/mL) (p < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Blood Circulation; Blood Pressure; Creatinine; Dopamine; Endothelins; Epinephrine; Female; Hemodynamics; Hemofiltration; Humans; Lactates; Lactic Acid; Male; Middle Aged; Norepinephrine; Renin; Sepsis; Time Factors; Vascular Resistance; Vasopressins; Wounds and Injuries

Plasma alpha-atrial natriuretic peptide (alpha-ANP) concentrations were measured during mechanical ventilation in nine patients with acute respiratory failure (ARF) associated with sepsis. The relationships between alpha-ANP and pulmonary hemodynamic variables were examined. A total of 22 measurements of alpha-ANP and other variables were obtained. The mean plasma alpha-ANP concentration of 22 measurements was 120.1 +/- 79.8 pg/ml (normal 31.7 +/- 12.0, mean +/- SD). Plasma alpha-ANP concentrations correlated with mean pulmonary artery pressure (MPAP) (r = .703, p less than .01) and pulmonary vascular resistance (PVR) (r = .606, p less than .01), but not with other variables. These findings suggest that alpha-ANP elevation may be related to the increases in MPAP and PVR in ARF associated with sepsis.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Humans; Middle Aged; Pulmonary Artery; Respiration, Artificial; Respiratory Insufficiency; Sepsis; Vascular Resistance