atrial-natriuretic-factor and Shock--Septic

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

Aside from its established immunologic and hematologic functions, the spleen also plays an important role in cardiovascular regulation. This occurs through changes in intrasplenic microvascular tone, as well as through splenic neurohormonal modulation of the renal and mesenteric vascular beds. Splenic regulation of blood volume occurs predominantly through fluid extravasation from the splenic circulation into lymphatic reservoirs; this is controlled by direct modulation of splenic pre- and postcapillary resistance by established physiologic agents such as atrial natriuretic peptide (ANP), nitric oxide (NO), and adrenomedullin (ADM). In addition to physiologic fluid regulation, splenic extravasation is a key factor in the inability to maintain adequate intravascular volume in septic shock. The spleen also controls renal microvascular tone through reflex activation of the splenic afferent and renal sympathetic nerves. This splenorenal reflex not only contributes to the physiologic regulation of blood pressure, but also contributes to the cardiovascular dysregulation associated with both septic shock and portal hypertension. In septic shock, the splenorenal reflex protectively limits splenic extravasation and potentially promotes renal sodium and water reabsorption and release of the vasoconstrictor angiotensin II; this function is eventually overwhelmed as shock progresses. In portal hypertension, on the other hand, the splenorenal reflex-mediated reduction in renal vascular conductance exacerbates sodium and water retention in the kidneys and may eventually contribute to renal dysfunction. Preliminary evidence suggests that the spleen also may play a role in the hemodynamic complications of portal hypertension via neurohormonal modulation of the mesenteric vascular bed. Lastly, the spleen itself may be a source of a vasoactive factor.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension, Portal; Kidney; Nitric Oxide; Shock, Septic; Splanchnic Circulation; Spleen

Central and renal hemodynamics, renal oxygenation, renal uptake of glucose, lactate, fats, renal carnitine metabolism, arterial atrial natriuretic factor (ANF) and catecholamine release were studied in sixteen adult beagle dogs during pentobarbital anesthesia. Renal cortical oxygen tension was recorded by means of a Silastic tonometer. Twelve animals underwent acute circulatory shock induced by intravenous Escherichia coli endotoxin 0.5 mg/kg. Four control dogs received normal saline. The endotoxin infusion resulted in decreased cardiac function, renal blood flow and renal cortical PO2. The renal venous PO2 increased during the experiment. Arterial and renal venous glucose concentrations increased transiently during endotoxemia. Circulating lactate concentrations increased significantly whereas the arteriovenous lactate difference remained almost unchanged. Renal uptake of lactate and glucose were not influenced during the moderate renal hypoperfusion caused by endotoxin. Arterial free fatty acid (FFA) concentrations increased significantly 2 hours after onset of the endotoxin infusion whereas renal venous FFA levels remained rather stationary. The renal uptake of FFA increased with increasing arterial FFA concentrations. Circulating free carnitine concentrations increased significantly in endotoxin shock. Blood acyl-carnitine concentrations remained essentially unchanged. Carnitine concentrations declined significantly in endotoxic renal tissue. The arterial concentrations of ANF, epinephrine, norepinephrine and the norepinephrine metabolite 3,4-dihydroxyphenylglycol (DHPG) increased in plasma during early endotoxemia. The levels of these hormones remained very low and constant in the controls. To summarize, endotoxin injection resulted in impaired renal perfusion and oxygenation, increased uptake of free fatty acids and unchanged uptake of glucose, lactate, glycerol and triglycerides. Decreased renal carnitine concentrations were observed. Arterial plasma concentrations of ANF and catecholamines increased in endotoxin shock.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Carnitine; Catecholamines; Dogs; Energy Metabolism; Fatty Acids, Nonesterified; Glycerol; Humans; Kidney; Lactates; Oxygen Consumption; Renal Circulation; Shock, Septic; Triglycerides

To investigate the physiologic effects of exogenous vasopressin as a potential alternative to traditional high-dose catecholamine therapy for septic patients with vascular hyporeactivity to catecholamines.. Prospective, case-controlled study.. Intensive care unit of a university hospital.. Vasopressin was infused in 16 critically ill septic patients who remained persistently hypotensive despite infusions of pharmacologic doses of catecholamines.. Continuous intravenous infusion of vasopressin at 0.04 units/min for 16 hrs, in place of escalating the amount of catecholamines being infused.. After administration of vasopressin, systemic vascular resistance and mean arterial pressure were immediately and significantly increased in comparison with the values obtained just before vasopressin. When the vasopressin infusions were discontinued, mean arterial pressure decreased immediately and dramatically. We did not detect any obvious adverse cardiac effects during the vasopressin infusions. Vasopressin had no effect on other hemodynamic parameters or any of the metabolic parameters studied, including measures of oxygenation, plasma glucose, or electrolytes. Urine output increased significantly during the administration of vasopressin, although this effect may be nonspecific. Lactate concentrations decreased, particularly in the survival group, but the decreases were not significant. Overall survival was 56%.. Low-dose vasopressin infusions increased mean arterial pressure, systemic vascular resistance, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines. The data indicate that low-dose vasopressin infusions may be useful in treating hypotension in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Gas Analysis; Blood Glucose; Critical Illness; Drug Monitoring; Electrolytes; Female; Hemodynamics; Humans; Infusions, Intravenous; Lactic Acid; Male; Middle Aged; Prospective Studies; Renin; Shock, Septic; Survival Analysis; Time Factors; Vasoconstrictor Agents; Vasopressins

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

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

Risk stratification could represent a major improvement in critically ill patients' management. The objective of this study is to evaluate the association between concentrations of four circulating prohormones (C-terminal-provasopressin, midregional-proadrenomedullin (MR-proADM), midregional-proatrial natriuretic peptide, and C-terminal- proendothelin-1) and the occurrence of nosocomial infections (NIs) in septic shock patients.. We performed an observational, clinical study with septic shock patients (n = 98) recruited from adult intensive care units in a university hospital. Prohormone concentrations were assessed three times within the first week after the onset of septic shock using an immunoluminometric assay.. Significantly elevated plasmatic MR-proADM concentrations were measured in patients who went on to develop NIs in comparison with patients who remain infection free (p = 0.043). No differences were observed for the other three prohormone concentrations.. Elevated plasmatic MR-proADM concentration is associated with the development of secondary NIs after septic shock. This information, if confirmed in a larger group of patients, could represent a major advance in the monitoring of intensive care unit patient infectious risk.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Cohort Studies; Cross Infection; Endothelin-1; Female; Glycopeptides; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Risk Factors; Severity of Illness Index; Shock, Septic

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

Septic shock is a major health care problem that affects a heterogeneous population of patients. To improve sepsis management, a key point is to decrease this heterogeneity by stratifying patients according to specific criteria, such as appropriate biomarkers. As the early phase of septic shock is characterized by cardiovascular dysfunction, precursors of vasoactive hormones represent interesting candidates. The objective of the present study was to concomitantly assess the predictive value of C-terminal proendothelin-1 and midregional proatrial natriuretic peptide (CT-proET-1 and MR-proANP, respectively vasoconstrictor and vasodilator) on 28-day mortality following septic shock.. In this observational study which included 99 patients, concentrations of MR-proANP and CT-proET-1 were measured using an immunoluminometric assay three times within the first week after the onset of septic shock.. While MR-proANP concentrations were significantly increased in non-survivors in comparison with survivors, no differences were noted for CT-proET-1. Increased MR-proANP concentrations were significantly associated with mortality after both univariate and multivariate analyses, adjusted for usual clinical confounders [SAPS II (simplified acute physiology score II), SOFA (sepsis-related organ failure assessment) scores and number of co-morbidities].. In septic shock patients, MR-proANP appears to be a good predictor of 28-day mortality, whereas CT-proET-1 does not present any predictive value during monitoring.

Topics: Atrial Natriuretic Factor; Biomarkers; Endothelin-1; Humans; Immunoassay; Mortality; Observation; Predictive Value of Tests; Prognosis; Protein Precursors; Shock, Septic; Survivors

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Endotoxemia; Glucocorticoids; Hormones; Humans; Inflammation Mediators; Neurophysins; Prednisolone; Protein Precursors; Shock, Septic; Vasopressins

Atrial natriuretic peptide (ANP) is a hormone secreted in response to atrial or ventricular volume expansion and pressure overload, respectively. However, it has been found in studies with animals and patients an increase in ANP plasma concentration, during advanced septic shock, despite the fall in mean arterial pressure (MAP). Several studies support the hypothesis that NO may be involved in the regulation of ANP release. Since NO may have an effect on ANP release, we hypothesized that NO pathway may participate in the control of the ANP release induced by the endotoxemic shock. Thus, the purpose of the present study was to assess the effect of the intravenous (i.v.) and intracereboventricular (i.c.v.) administration of aminoguanidine, an iNOS blocker, on plasma ANP levels and MAP during experimental endotoxemic shock. Experiments were performed on adult male Wistar rats weighing 180-240 g. Rats were injected i.v. by bolus injection with 1.5 mg/kg of Lipopolysaccharide (LPS) or saline (0.5 mL) and were decapitated 2, 4 and 6 h after LPS injection for ANP determination by radioimmunoassay. In a separate set of experiments, rats received intravenous (i.v.) (100 mg/kg) or intracerebroventricular (i.c.v.) (250 microg in a final volume of 2 microL) injection of aminoguanidine (AG). Thirty minutes after the i.c.v. or i.v. injections, animals received LPS and were decapitated 2, 4 and 6 h later to determine plasma ANP concentration. In the two set of experiments MAP and heart rate (HR) were measured each 15 min for a period of 6 h using a polygraph. When animals were injected with LPS, a reduction (p<0.01) in MPA and an increase in HR occurred. A significant increase in plasma ANP concentration occurred, coinciding with the period of drop in blood pressure. We found a significant increase in plasma ANP concentration after AG plus LPS injection, when compared to the rats treated with LPS plus saline. Further, the administration of AG plus LPS attenuated the decrease in the MAP after LPS and attenuated the increase in the HR when compared to the rats treated with LPS plus saline. Our study suggests that inducible NOS pathway may activate an inhibitory control mechanism that attenuates ANP secretion, which is not regulated by the changes in blood pressure.

Topics: Animals; Atrial Natriuretic Factor; Enzyme Inhibitors; Guanidines; Lipopolysaccharides; Male; Nitric Oxide Synthase Type II; Rats; Rats, Wistar; Shock, Septic

Our objective was to investigate the plasma levels of brain and atrial natriuretic peptides (BNP and ANP, respectively) in patients with septic shock/severe sepsis and to study the association of BNP and ANP levels with hemodynamic parameters, severity of the disease, and prognosis of those patients. This is a prospective case series study of 22 patients with septic shock, 11 patients with severe sepsis, and 20 healthy volunteers at the Department of Emergency and Critical Care Medicine, Nara Medical University Hospital, Japan. Blood collection was performed on admission and on days 1, 2, and 4. Plasma BNP and ANP levels were measured by radioimmunoassay. Right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, and left ventricular stroke work index were determined using a thermodilution catheter. Acute Physiological and Chronic Health Evaluation II scores were calculated. Plasma levels of BNP and ANP were markedly elevated in patients with septic shock/severe sepsis compared with controls (BNP, 7 +/- 0.3 pg mL; ANP, 13 +/- 1 pg mL). In patients with septic shock, both BNP and ANP peaked on day 2 (BNP, 987 +/- 160 pg mL; ANP, 103 +/- 17 pg mL). Plasma levels of BNP on day 2 in patients with septic shock significantly correlated with right atrial pressure (r = 0.744, P < 0.01), mean pulmonary arterial pressure (r = 0.670, P < 0.01), pulmonary arterial wedge pressure (r = 0.709, P < 0.01), left ventricular stroke work index (r = -0.552, P < 0.05), Acute Physiological and Chronic Health Evaluation II score (r = 0.581, P < 0.01), and poor prognosis (P < 0.05). The optimal cutoff point for predicting mortality in patients with septic shock was a BNP level of 650 pg mL on day 2, in which sensitivity and specificity were 92% and 80%, respectively. Increased plasma levels of BNP may reflect not only the severity of myocardial depression but also the disease severity and could be of prognostic value in patients with septic shock.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Fluid Therapy; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Reference Values; Respiratory Distress Syndrome; Severity of Illness Index; Shock, Septic

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

Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock.. Retrospective, clinical study in the medical intensive care unit of a university hospital.. 17 patients with septic shock and 19 control subjects.. Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days.. In septic shock we found a significant increase in ANP (82.7+/-9.9 vs. 14.9+/-1.2 pg/ml) and BNP (12.4+/-3.6 vs. 5.5+/-0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=-0.56; p<0.05).. ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.

Topics: Atrial Natriuretic Factor; Female; Follow-Up Studies; Humans; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Shock, Septic; Time Factors; Ventricular Dysfunction, Left

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

To assess the value of alpha-atrial natriuretic peptide (alpha-ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock.. Prospective observational study.. Medical intensive care unit (ICU) of a university hospital.. Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place.. Hemodynamic variables and plasma levels of alpha-ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m2 in all patients, and the median peak circulating alpha-ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/mL) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha-ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak alpha-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m2) was for alpha-ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for alpha-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha-ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively.. Circulating alpha-ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Cyclic GMP; Endothelins; Female; Hemodynamics; Humans; Male; Middle Aged; Netherlands; Prognosis; Prospective Studies; Respiratory Mechanics; Sensitivity and Specificity; Shock, Septic; Statistics, Nonparametric; Survival Rate; Ventricular Function

To investigate the vascular smooth muscle dysfunction of septic shock, in vitro isometric responses to phenylephrine (PE) and acetylcholine (ACh) were evaluated in aortic rings, with and without endothelium (+/-E), removed from male Wistar rats 1.5, 3 and 6 h after intravenous (i.v.) administration of 5 mg/ kg lipopolysaccharide (LPS) or vehicle. A reduction in maximum contraction (+/-E) and sensitivity (-E) to PE were identified at 6 but not at 1.5 or 3 h. Maximum relaxation to ACh (+E) was not affected by LPS treatment but sensitivity was increased at 1.5 and 3 h. Having identified 6 h as the time at which the most pronounced changes were observed, further studies at this interval found that maximum contraction to potassium chloride (+/-E), prostaglandin F2 alpha (+E) and detomidine (-E) and relaxation to salbutamol (-E) were less in aortic rings from endotoxaemic rats. Sensitivity to KCl (+/-E), PGF2 alpha (-E) and detomidine (-E) was also reduced. Relaxation to sodium nitroprusside and atrial natriuretic peptide was not changed. These results suggest that attenuated pressor responses to a variety of vasoactive agents may be expected in patients 6 h after systemic exposure to endotoxin and that this vasoplegia may influence the vascular side-effects of therapeutic agents.

Topics: Acetylcholine; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Albuterol; Analysis of Variance; Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Imidazoles; Injections, Intravenous; Isometric Contraction; Lipopolysaccharides; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroprusside; Phenylephrine; Potassium Chloride; Rats; Rats, Wistar; Shock, Septic; Vasodilator Agents

To determine if there are changes in circulating concentrations of endogenous atrial natriuretic peptide and the physiologic role of this peptide in endotoxic shock.. A prospective, randomized, controlled animal trial.. University research laboratory.. Anesthetized male Wistar rats, weighing 250 to 350 g.. Six rats received 1.5 mg/kg body weight of lipopolysaccharide alone. Five rats received 1.5 mg/kg of lipopolysaccharide and 200 microL/100 g body weight of rabbit anti-atrial natriuretic peptide serum. Another five rats received 1.5 mg/kg of lipopolysaccharide and normal rabbit serum in the same volume as the antiserum.. Plasma concentrations of atrial natriuretic peptide, arginine vasopressin, and aldosterone were measured, and changes in hemodynamic parameters and renal function were monitored in rats with endotoxic shock after catheterization of the right jugular vein. Urine volume, urine sodium excretion, urinary potassium excretion, and urine 3', 5'-cyclic guanosine monophosphate (cGMP) excretion were measured at 12-hr intervals. The plasma atrial natriuretic peptide concentration was slightly but significantly lower 30 mins after the lipopolysaccharide injection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01) and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL, p < .01 vs. 0 time) and remaining at higher concentrations than before the preinjection value, up to 24 hrs. In contrast, acute spike-like increases of arginine vasopressin and aldosterone concentrations were observed 30 mins after the lipopolysaccharide injection, preceding the increase of the plasma atrial natriuretic peptide concentration. Measurements of urine volume and urine sodium excretion showed oliguria during the initial 12 hrs after the lipopolysaccharide injection, followed by diuresis and natriuresis during the subsequent 12 hrs. In addition, injection with anti-atrial natriuretic peptide serum in the diuretic phase 12 hrs after the lipopolysaccharide injection significantly inhibited the diuresis, natriuresis, and urine cGMP excretion in this model. Furthermore, the plasma aldosterone concentration 24 hrs after the lipopolysaccharide injection was significantly increased by the administration of the antisera.. These findings suggest that endogenous atrial natriuretic peptide increases in the acute phase of endotoxic shock and plays an important role in water and electrolyte balance by regulating diuresis.

Topics: Aldosterone; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Diuresis; Hematocrit; Immune Sera; Lipopolysaccharides; Male; Natriuresis; Prospective Studies; Rats; Rats, Wistar; Shock, Septic

Nitric oxide and atrial natriuretic peptides are the main activators of guanylyl cyclases, which transform GTP into cyclic GMP and thereby contribute to the decrease of vascular tone. To investigate the increase, if any, of plasma cyclic GMP concentrations in human patients with hyperdynamic circulation resulting from acute liver failure and to ascertain whether guanylyl cyclase activation is involved in the decline of systemic vascular resistance that occurs in this pathophysiological condition, we simultaneously recorded hemodynamic data and cyclic GMP levels in patients with fulminant liver failure before and after liver transplantation and in normokinetic patients undergoing abdominal nonseptic surgery. We also compared these data with those recorded in patients with hyperkinetic shock resulting from gram-negative sepsis or nitric oxide-independent vasomotor agent (carbamate) over-dose. In all these patients we simultaneously studied kidney function, platelet counts and atrial natriuretic peptides. Patients with fulminant liver failure had higher cyclic GMP concentrations than did control patients undergoing abdominal surgery (11.02 +/- 1.55 pmol.ml-1 vs. 1.77 +/- 0.18 pmol.ml-1, p < 0.001). At similar heart-loading conditions these concentrations were lower than those in gram-negative septic shock (18.2 +/- 1.35 pmol.ml-1, p < 0.05) but higher than those in carbamate-induced shock (3.6 +/- 0.7 pmol.ml-1, p < 0.01). In addition, cyclic GMP concentrations significantly decreased from the fulminant liver failure period to the posttransplantation period, although atrial natriuretic peptide levels did not change significantly and kidney function worsened.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Blood Circulation; Carbamates; Cyclic GMP; Female; Guanylate Cyclase; Hemodynamics; Hepatic Encephalopathy; Humans; Kidney; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Platelet Count; Prospective Studies; Shock; Shock, Septic; Vascular Resistance

We have previously reported that C-type natriuretic peptide (CNP), the third member of natriuretic family, was produced in vascular endothelial cells and hypothesized that CNP might be a local regulator of vascular tone and/or growth from endothelial cells. In order to clarify the pathophysiological significance of CNP in humans, we examined the presence of CNP in human circulation and determined plasma levels of CNP in patients with various cardiovascular disorders. The plasma level of CNP in healthy persons was 1.4 +/- 0.6 fmol/ml (n = 13). The plasma level of CNP was markedly increased in patients with septic shock (13.2 +/- 10.1 fmol/ml, n = 11), while there was no alteration in patients with congestive heart failure or hypertension. There was two-fold increase of the plasma CNP level in patients with chronic renal failure. These results indicate that CNP, which can be considered as an endothelium-derived relaxing peptide, is detectable in human circulation and suggest the pathophysiological significance of endothelial CNP in humans.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Chromatography, Gel; Chromatography, High Pressure Liquid; Cross Reactions; Heart Failure; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Reference Values; Shock, Septic

Topics: Aged; Atrial Natriuretic Factor; Endothelins; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Radioimmunoassay; Shock, Septic

On the isolated perfused heart model of septic rats, the present study showed that: (1) Calcium content and 45Ca-influx of myocardium increased 190%, 208% (P < 0.01) and that of mitochondria elevated 332%, 178% (P < 0.01) respectively with no change of myocardial 45Ca-release during sepsis. (2) 10(-8) mol/L calcitonin gene-related peptide (CGRP) or 10(-7) mol/L atriopeptin (ANP) added into the Krebs-Henseleit solution could effectively reduce 45Ca-influx to myocardium and mitochondria with no effect on myocardial 45Ca-release. (3) The calcium uptake reserve of mitochondria evaluated in vitro showed that the maximal calcium uptake and uptake velocity of mitochondria during sepsis were reduced 34.6%, 33.3% (P < 0.01) respectively. The data suggested that the net increase of myocardial Ca2+ content resulted from increase of 45Ca-influx with no change of 45Ca-efflux and the reduction of mitochondrial Ca2+ buffering capacity during sepsis were key events in the pathogenesis of intracellular Ca(2+)-overload. CGRP and ANP could effectively alleviate Ca(2+)-overload of myocardium and mitochondria. This may have some cellular protection action during sepsis.

Topics: Animals; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Calcium; In Vitro Techniques; Male; Mitochondria, Heart; Myocardium; Rats; Rats, Wistar; Shock, Septic

To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR).. Prospective clinical investigation.. Medical intensive care unit of a university hospital.. 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and--in some cases--hemodialysis.. Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84 +/- 1.52 pmol.ml-1) than in healthy controls (1.77 +/- 0.18 pmol.ml-1, p < 0.0001), in septicemia patients without circulatory failure (3.28 +/- 0.36 pmol.ml-1, p < 0.005) or in patients with hyperkinetic non-septic shock (3.6 +/- 0.7 pmol.ml-1, p < 0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP.. These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Female; Humans; Male; Middle Aged; Platelet Count; Prospective Studies; Shock, Septic; Vascular Resistance

Topics: Animals; Atrial Natriuretic Factor; Dogs; Hormones; Shock, Septic