atrial-natriuretic-factor and Respiratory-Distress-Syndrome

The increased understanding of the pathophysiology of ALI that has been achieved over the last decade has led to several new pharmacologic approaches for the prevention and management of ALI and ARDS. Based on in vitro information and animal model data, many of these strategies seem quite compelling. Nevertheless, to date, no specific pharmacologic approach for the prevention or treatment of ARDS has been conclusively validated in clinical trials. Active basic and clinical research continues, and it is hoped that these investigations will lead to new therapies that can be applied by the clinician to improve clinical outcomes for patients who have ALI and ARDS.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antioxidants; Atrial Natriuretic Factor; Humans; Ketoconazole; Pentoxifylline; Protein C; Recombinant Proteins; Respiratory Distress Syndrome

To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal.. Prospective study.. Surgical intensive care unit, university hospital.. Patients with acute lung injury and right ventricular failure.. Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days).. The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy.. Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.

Topics: Administration, Inhalation; Adult; Aged; Atrial Natriuretic Factor; Cyclic GMP; Endothelin-1; Endothelium-Dependent Relaxing Factors; Female; Humans; Intensive Care Units; Male; Middle Aged; Nitric Oxide; Respiratory Distress Syndrome; Ventricular Dysfunction, Right

To study the effects of infusion of atrial natriuretic peptide (ANP) versus the inhalation of nitric oxide (NO) in patients with an early acute respiratory distress syndrome (ARDS).. Ten patients with severe ARDS were studied in a crossover study design, within 72 hours after starting mechanical ventilation. We studied the effects of ANP infusion (10 ng/kg/min for 1 hour) and of inhalation of NO (20 ppm for 1 hour) on hemodynamic and respiratory patient parameters, as well as the effects on plasma levels of ANP, guanosine 3',5'-cyclic monophosphate, nitrate and endothelin-1.. Despite an approximate 50% increase in mixed venous ANP plasma concentration (from 86 +/- 21 to 123 +/- 33 ng/l, P < 0.05) during ANP infusion, there were no changes in mean pulmonary artery pressure, pulmonary vascular resistance index, extravascular lung water index, or in pulmonary gas exchange. NO inhalation, in contrast, lowered mean pulmonary artery pressure (from 26 +/- 1.9 to 23.9 +/- 1.7 mmHg, P < 0.01), pulmonary vascular resistance index (from 314 +/- 37 to 273 +/- 32 dynes/cm5/m2, P < 0.05) and central venous pressure (from 8.2 +/- 1.2 to 7.3 +/- 1.1 mmHg, P < 0.02). Furthermore, NO inhalation improved pulmonary gas exchange, reflected by a decrease in alveolar-arterial oxygen gradient (from 41.9 +/- 3.9 to 40.4 +/- 3.6 kPa, P < 0.05), a small increase in oxygenation (PaO2/FiO2 from 17.7 +/- 1.4 to 19.7 +/- 1.1 kPa, P = 0.07) and a small decrease in venous admixture (Qs/Qt from 35.7 +/- 2.0 to 32.8 +/- 2.7%, P = 0.11).. This study shows that, in contrast to NO inhalation, infusion of ANP neither improves oxygenation nor attenuates pulmonary hypertension or pulmonary edema in patients with severe ARDS.

Topics: Administration, Inhalation; Adult; Aged; Atrial Natriuretic Factor; Cross-Over Studies; Cyclic GMP; Endothelin-1; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Nitrates; Nitric Oxide; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Vasodilator Agents

The purpose of this study was to investigate the effect of i.v. infusion of atrial natriuretic peptide (ANP) on hemodynamics, pulmonary gas exchange, and urine volume during mechanical ventilation with positive end-expiratory pressure (PEEP) in patients with acute lung injury.. Prospective, randomized, comparable study.. ICU of a university hospital.. Forty patients with moderate acute lung injury (lung injury score > or = 2.0) who required mechanical ventilation with PEEP were studied.. The patients were randomly divided into two groups: ANP group (n=20) and control group (n=20). The ANP group received genetic recombination alpha-human ANP (carperitide) at the rate of 0.1 microg/kg/min for 24 h. The control group did not receive ANP.. Hemodynamic and blood gas parameters, and urine volume were measured at baseline, 3 h, and 24 h after initiating the ANP infusion. Plasma ANP concentrations markedly (p<0.01) increased from 112.0+/-27.0 to 1,868.3+/-385.3 pg/mL after 24 h in the ANP group, whereas they remained unchanged in the control group. In the ANP group, hemodynamic parameters did not change, but PaO2/FIO2 (fraction of inspired oxygen) and thoracic compliance significantly (p<0.01) increased at 24 h after initiating the ANP infusion, associated with significant (p<0.01) decreases in lung injury score and shunt. Urine volume significantly (p<0.01) increased during 0 to 3 h after initiating the ANP infusion. In the control group, hemodynamics, pulmonary gas exchange, and urine volume did not significantly change during the study period. There were significant differences in PaO2/FIO2 (24 h), thoracic compliance (24 h), lung injury score (24 h), and urine volume (3 h) between the two groups.. The results suggest that ANP infusion induces diuresis and improves pulmonary gas exchange in patients with acute lung injury during mechanical ventilation with PEEP.

Topics: Aged; Aged, 80 and over; Airway Resistance; Atrial Natriuretic Factor; Bronchodilator Agents; Carbon Dioxide; Diuretics; Female; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Oxygen; Oxygen Consumption; Peptide Fragments; Positive-Pressure Respiration; Prospective Studies; Pulmonary Gas Exchange; Pulmonary Ventilation; Recombinant Proteins; Respiratory Distress Syndrome; Respiratory Mechanics; Thorax; Urine

Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in managing Covid-19.

Topics: Aldosterone; Aminobutyrates; Anti-Inflammatory Agents; Atrial Natriuretic Factor; Biphenyl Compounds; Cathepsin G; COVID-19 Drug Treatment; Cytokines; Gastrin-Releasing Peptide; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Neprilysin; Renin; Respiratory Distress Syndrome; Tetrazoles; Valsartan

Plasma atrial natriuretic peptide levels (proANP (1-98)), a parameter of myocardial dysfunction, have been reported to be increased in critically ill patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The aim of the study was to examine if proANP is a biomarker of ALI/ARDS as assessed by the Sequential Organ Failure Assessment score (SOFA Lung ≥2) in burn patients, and how it compares to the corresponding values for age, total body surface area percent (TBSA%) and inhalation injury for mortality prediction.. A group of 22 burn patients with a mean TBSA of 30% (10-75%) and a mean age of 52 years (25-84 years) was investigated during 2010. Organ dysfunction/failure was classified according to the SOFA score. The criteria for ALI/ARDS were based on SOFA Lung ≥2. ProANP (1-98) concentrations (nmoll(-1)) were measured by commercially available enzyme linked immunosorbent assay (ELISA) immunoassays (Biomedica Austria) on post-burn days 2 and 7.. ProANP levels on day 7 post-burn positively correlated with a SOFA score day 7 post-burn, c=0.91. The receiver operating curve (ROC) analysis proved a sensitivity of 75% and a specificity of 75% for ALI/ARDS at cut-off values >3.35 nmoll(-1). The ROC value of proANP for ALI/ARDS (SOFA Lung ≥2) was significantly larger than that of age, TBSA% and inhalation injury: 0.90, 0.71, 0.74, and 0.69 (p<0.001).. ProANP levels, as a biomarker of ALI/ARDS, in critically burn patients correlated with SOFA scoring. The inhalation injury did not lead to increase in proANP values.

Topics: Acute Lung Injury; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Burns; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Regression Analysis; Respiratory Distress Syndrome; ROC Curve; Sensitivity and Specificity

The response to inhaled nitric oxide (iNO) is inconsistent in patients with acute respiratory distress syndrome (ARDS). We sought to determine whether the response to iNO, defined as 20% Pao(2)/Fio(2) increase from baseline, depends on the level of cardiac natriuretic peptides.. This is a prospective cohort study including 11 consecutive patients with ARDS who were eligible to receive iNO. Measurements of plasma concentrations of atrial natriuretic peptide (ANP), N-Terminal-Pro-B-Type Natriuretic Peptide (NT-pro-BNP) and 3',5'-cyclic guanosine monophosphate were obtained before initiating iNO and 30 minutes later during iNO. Baseline cardiac peptides, oxygenation, and hemodynamic variables and their change during iNO were compared among responders and nonreponders to iNO.. Baseline ANP and NT-pro-BNP concentrations were higher in patients that responded to iNO and tended to decrease during iNO in responders only. 3',5'-Cyclic guanosine monophosphate concentrations were not different among responders and nonresponders and were unchanged during iNO. Baseline ANP was strongly correlated with change in intrapulmonary shunt, and baseline NT-pro-BNP and its change were correlated with the change in cardiac output.. High ANP and NT-pro-BNP concentrations are associated with the response to iNO. These data suggest that cardiac peptides have the potential to identify a subgroup of patients with ARDS who might derive clinical benefit from iNO.

Topics: Administration, Inhalation; Adolescent; Adult; Atrial Natriuretic Factor; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Prospective Studies; Respiratory Distress Syndrome; Risk Factors; Treatment Outcome; Young Adult

Ischemia-reperfusion (IR) causes human lung injury in association with the release of atrial and brain natriuretic peptides (ANP and BNP), but the role of ANP/BNP in IR lung injury is unknown. ANP and BNP bind to natriuretic peptide receptor-A (NPR-A) generating cGMP and to NPR-C, a clearance receptor that can decrease intracellular cAMP. To determine the role of NPR-A signaling in IR lung injury, we administered the NPR-A blocker anantin in an in vivo SWR mouse preparation of unilateral lung IR. With uninterrupted ventilation, the left pulmonary artery was occluded for 30 min and then reperfused for 60 or 150 min. Anantin administration decreased IR-induced Evans blue dye extravasation and wet weight in the reperfused left lung, suggesting an injurious role for NPR-A signaling in lung IR. In isolated mouse lungs, exogenous ANP (2.5 nM) added to the perfusate significantly increased the filtration coefficient sevenfold only if lungs were subjected to IR. This effect of ANP was also blocked by anantin. Unilateral in vivo IR increased endogenous plasma ANP, lung cGMP concentration, and lung protein kinase G (PKG(I)) activation. Anantin enhanced plasma ANP concentrations and attenuated the increase in cGMP and PKG(I) activation but had no effect on lung cAMP. These data suggest that lung IR triggered ANP release and altered endothelial signaling so that NPR-A activation caused increased pulmonary endothelial permeability.

Topics: Animals; Atrial Natriuretic Factor; Cell Adhesion Molecules; Cyclic AMP; Cyclic GMP; Guanylate Cyclase; Lung; Male; Mice; Mice, Inbred Strains; Microfilament Proteins; Perfusion; Phosphoproteins; Receptors, Atrial Natriuretic Factor; Reperfusion Injury; Respiratory Distress Syndrome; Signal Transduction

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

Topics: Acute Disease; Atrial Natriuretic Factor; Diagnosis, Differential; Dyspnea; Heart Failure; Humans; Natriuretic Peptide, Brain; Respiratory Distress Syndrome; Respiratory Insufficiency

To clarify how plasma atrial natriuretic peptide concentrations vary with the severity of acute lung injury. The influence of coexisting diseases which trigger acute lung injury was also examined.. Prospective study.. Intensive care unit of a university hospital.. Fifty patients who had standard risk factors for acute lung injury including sepsis syndrome, major surgery, prolonged hypotension, aspiration of gastric contents, and burns. Twenty-five of these patients had acute lung injury (group 3) caused by these disorders; the remaining 25 patients had risk factors only (group 2). Ten age-matched normal volunteers were selected as controls (group 1).. None.. Plasma atrial natriuretic peptide concentration was measured in these patients and compared with the severity of acute lung injury. In group 3, a significant increase in the mean plasma atrial natriuretic peptide concentration was observed (188 +/- 78 pg/mL, p < .01) compared with group 2 (54 +/- 28 pg/mL) and the age-matched control group (30 +/- 8 pg/mL). This increase was related to the onset of acute lung injury and returned to control concentrations after recovery. Plasma atrial natriuretic peptide concentrations in group 3 correlated highly with a lung injury score representing the severity of acute lung injury (r2 = .45, p < .01), but did not correlate with other cardiopulmonary variables.. The results suggest that severity of lung injury, but not other predisposing disorders, may be the key factor leading to the increase in plasma atrial natriuretic peptide concentrations observed in these patients.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Burns; Comorbidity; Hemorrhage; Humans; Hypotension; Japan; Linear Models; Pneumonia, Aspiration; Prospective Studies; Respiratory Distress Syndrome; Risk Factors; Systemic Inflammatory Response Syndrome

We measured plasma atrial natriuretic factor over the clinical course of 12 patients with the adult respiratory distress syndrome (ARDS). A total of 33 sequential measurements were correlated with 23 hemodynamic, pulmonary, and renal parameters. Atrial natriuretic factor was found to be eight times higher than age-matched healthy control subjects (p = 0.001). Although atrial natriuretic factor correlated well with pulmonary capillary wedge pressure (r = 0.592), there was no significant relationship between right atrial pressure and plasma atrial natriuretic factor (r = 0.258). Atrial natriuretic factor was best related to pulmonary artery systolic pressure (r = 0.751). We conclude that in ARDS, plasma atrial natriuretic factor is markedly elevated and arterial levels are best determined by left atrial pressure and pulmonary hemodynamics, and not by right sided cardiac pressures. The role of increased circulating atrial natriuretic factor in the pathophysiology of ARDS is to be clarified in future studies.

Topics: Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Humans; Male; Pulmonary Artery; Pulmonary Circulation; Pulmonary Wedge Pressure; Respiratory Distress Syndrome

The influence of PEEP during controlled mechanical ventilation (CMV) on plasma levels of alpha-atrial natriuretic peptide (alpha-ANP) was examined in seven patients suffering from acute respiratory failure. The majority of patients were volume-expanded. Samples were drawn from the superior vena cava, right atrium, pulmonary artery, and radial artery. All alpha-ANP levels were significantly depressed by 15 cm H2O PEEP for one hour, when compared to CMV without PEEP. During the PEEP period, cardiac index, creatinine clearance, urinary flow and urinary sodium excretion were decreased. CMV with PEEP of 20 cm H2O depressed peripheral venous plasma levels of alpha-ANP in six volume-expanded healthy volunteers, too. The decreased release of alpha-ANP could be a consequence of atrial compression by the distended lungs and of reduced venous return. We suggest that the decline in plasma alpha-ANP levels contributes to fluid retention and renal dysfunction, which occur frequently during CMV with PEEP. More detailed studies are necessary to confirm our hypothesis.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Male; Middle Aged; Radioimmunoassay; Respiration, Artificial; Respiratory Distress Syndrome

Topics: Animals; Arterioles; Atrial Natriuretic Factor; Female; Lung; Male; Oleic Acids; Rats; Rats, Inbred Strains; Respiratory Distress Syndrome

Although controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP) has a central place in the treatment of acute respiratory failure (ARF), several side effects of this technique have to be faced. CMV with PEEP may induce pulmonary barotrauma, disturbance of cardiac performance, impairment of renal function and fluid retention. Atrial natriuretic peptides (ANP) are released from the atria upon stretching and play a major role in the control of sodium and fluid balance. Therefore it was logical to determine plasma levels of alpha-ANP in CMV. A study performed in 7 patients suffering from ARF suggested that alpha-ANP plasma levels were depressed during PEEP at 15 cm H2O in comparison with PEEP at 0 cm H2O (ZEEP). The decrease in plasma levels of alpha-ANP was evident in samples taken from superior vena cava, right atrium, pulmonary artery and radial artery as well. The decrease in alpha-ANP was associated with a decline in cardiac index, creatinine clearance, urinary output and urinary sodium excretion. Experiments in volume- expanded healthy volunteers also suggest that CMV with PEEP is able to depress plasma levels of alpha-ANP. The reasons behind the decline in release of alpha-ANP may be atrial compression by the distended lungs and the well-known reduction of venous return to the heart. Other possible factors promoting fluid retention during CMV with PEEP are the decrease in cardiac index and glomerular filtration rate, changes in intrarenal distribution of blood flow, and a stimulation of release of antidiuretic hormone via stretch receptors in the left atrium and baroreceptors in aorta and carotid arteries.

Topics: Animals; Atrial Natriuretic Factor; Humans; Kidney; Positive-Pressure Respiration; Respiratory Distress Syndrome; Vasopressins; Water-Electrolyte Imbalance