endothelin-1 and Respiratory-Distress-Syndrome--Newborn

We measured exhaled nitric oxide and tracheal aspirate endothelin-1 to determine relationships between these substances and alterations in pulmonary gas exchange during respiratory distress syndrome (RDS) in comparison to those obtained from control preterm infants without RDS. Eight infants with RDS had measurements made at 24 hr and again at 48-72 hr. Eight control infants were studied once at 24-48 hr of life. Exhaled gas was analyzed on-line, and minute excretion of NO (V(NO)) was calculated. ET-1 was determined by immunoassay. Median V(NO) at 24 hr in RDS was 0.405 nl/min/kg (range, 0.30 -0.79), which subsequently declined by 48-72 hr to 0.166 nl/min/kg (P < 0.01). The V(NO) in RDS infants was significantly higher than time-matched V(NO) in controls, with a median of 0.099 nl/min/kg (range, 0.03-0.27; P < 0.001). ET-1 was not correlated with initial V(NO) in the RDS or control patients. In conclusion, in RDS, V(NO) decreases as gas exchange improves. ET-1 is detectable in tracheal aspirate samples in both groups of infants.

Topics: Body Fluids; Breath Tests; Endothelin-1; Humans; Infant, Newborn; Infant, Premature, Diseases; Intubation, Intratracheal; Nitric Oxide; Pulmonary Surfactants; Reference Values; Respiratory Distress Syndrome, Newborn; Respiratory Function Tests; Trachea

We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be used as a predictive marker for development of bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome.. This prospective observational study was done on 69 preterm neonates with gestational ages between 28 and 34 weeks and diagnosed as having respiratory distress syndrome. Serum concentrations of endothelin 1 was measured for all patients at day 3 of life and they were divided into BPD and No-BPD groups according to whether they developed bronchopulmonary dysplasia or not.. A total of 17 infants were in the BPD group and 52 infants were in the No-BPD group. Serum endothelin 1 was significantly higher in the BPD group (435.39±172.88) compared with the No-BPD group (302.65±49.32) (p < 0.001). Serum endothelin 1 correlated significantly with days spent on mechanical ventilation (r = 0.379, p = 0.022) and days spent on CPAP (r = 0.391, p = 0.001). A serum endothelin 1 cut off value of 302.7 ng/L could predict preterm that will develop bronchopulmonary dysplasia with a sensitivity of 88.24%, and specificity of 61.54%.. Serum endothelin 1 is significantly increased at day 3 of life in preterm neonates with respiratory distress syndrome who later develop bronchopulmonary dysplasia (BPD). It seems to be a promising predictive marker for BPD but further studies are needed to find the appropriate time for its measurement.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Decision Support Techniques; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Prospective Studies; Respiratory Distress Syndrome, Newborn; Severity of Illness Index

Plasma concentrations of the stable endothelin-1 precursor, C-terminal portion of the endothelin-1 precursor, determined prospectively in 293 newborn infants (gestational age, 24-41 weeks) at birth and on day 3 of life were unrelated to gestational age at birth, but strongly associated with respiratory distress when measured on day 3 of life.

Topics: Bronchopulmonary Dysplasia; Endothelin-1; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Respiratory Distress Syndrome, Newborn

In addition to the immaturity of air sacs and surfactant deficiency, preterm infants with respiratory distress syndrome (RDS) have abnormalities in the pulmonary vascular bed. We aimed to study two known modulators of pulmonary vessels: endothelin-1 (ET-1) and L-arginine. We hypothesized that plasma concentrations of ET-1 and L-arginine could correlate with the severity of RDS. We prospectively studied 71 preterm infants (gestational age = 29 to 35 weeks) with and without RDS. We measured plasma ET-1 by enzyme-linked immunosorbent assay and L-arginine by spectrophotometry. Infants who continued to require oxygen support or died by day of life 28 were considered to have bronchopulmonary dysplasia (BPD). ET-1 concentrations were significantly higher in RDS infants ( p = 0.039) than controls. Among infants with RDS, it was significantly higher in those who later developed BPD ( p = 0.026). L-arginine was significantly lower in RDS infants ( p = 0.001), but did not differ between BPD and non-BPD infants ( p = 0.19). There was no correlation between L-arginine and ET-1 ( r = 0.1, p = 0.41). The acute phase of RDS is associated with increased plasma concentrations of ET-1 and decreased L-arginine. Infants who later developed BPD had higher plasma ET-1 at birth. Concentrations of ET-1 and L-arginine did not correlate.

Topics: Arginine; Bronchopulmonary Dysplasia; Disease Progression; Endothelin-1; Female; Humans; Infant, Newborn; Infant, Premature; Logistic Models; Male; Prospective Studies; Respiratory Distress Syndrome, Newborn; Severity of Illness Index

Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.

Topics: Blotting, Western; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Cells, Cultured; Colon; Complement C5a; Connective Tissue Growth Factor; Endothelin-1; Female; Fibrosis; Green Fluorescent Proteins; Humans; Immunohistochemistry; Infant, Newborn; Lung; Male; Microscopy, Fluorescence; Myofibroblasts; Receptor, Anaphylatoxin C5a; Receptor, PAR-1; Receptors, Complement; Respiratory Distress Syndrome, Newborn; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Thrombin; Thromboplastin

The purpose of this present study was to evaluate the serum levels of ET-1 and TGF-beta in the newborns with respiratory distress. In this study, newborns with respiratory distress hospitalized into the Newborn Intensive Care Unit were included. The highest values of ET-1 and TGF-beta were obtained from newborns with diagnosis as meconium aspiration syndrome (5.70 +/- 5.87 pg/mL and 3.75 +/- 1.94 pg/mL, resp) in the sample obtained in the first six hours after birth, and these are statistically different from control group (P < .05). Also, same results were obtained for newborns with respiratory distress syndrome (3.37 +/- 1.59 pg/mL and 2.05 +/- 0.98 pg/mL, resp). After oxygen treatment, ET-1 values obtained in the first six hours of life were decreased regularly in the following days (P < .05). In the differentiating diagnosis of the respiratory distress of newborns, the investigation of ET-1 and TGF-beta levels is meaningful. The ET-1 levels investigated in the first six hours is more useful in determining the prognosis, and repeating ET-1 levels in the following days is more meaningful to determine clinical response.

Topics: Case-Control Studies; Diagnosis, Differential; Endothelin-1; Female; Humans; Infant, Newborn; Infant, Premature; Inflammation Mediators; Intensive Care Units, Neonatal; Male; Meconium Aspiration Syndrome; Respiratory Distress Syndrome, Newborn; Transforming Growth Factor beta; Turkey

Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 +/- 1.6 and 29.3 +/- 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

Topics: Analysis of Variance; Biomarkers; Case-Control Studies; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Respiratory Distress Syndrome, Newborn

Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P(ap)) during RDS may give insight in the role of ET-1.. ET-1 and P(ap) changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls.. Lung lavages induced a twofold increase of mean P(ap) (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P(ap), ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P(ap), in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration.. This experimental model of RDS shows that ET-1 concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled.

Topics: Animals; Animals, Newborn; Arteries; Blood Pressure; Carbon Dioxide; Disease Models, Animal; Endothelin-1; Hemodynamics; Humans; Hydrogen-Ion Concentration; Hypertension, Pulmonary; Infant, Newborn; Kinetics; Oxygen; Pulmonary Artery; Respiratory Distress Syndrome, Newborn; Sheep; Vascular Resistance

Endothelin-1 (ET-1) is a novel and potent endothelium-derived vasoconstriction peptide present in human plasma. In this study, plasma ET-1 concentrations were determined and their physiological significance was evaluated in Taiwanese neonates with respiratory distress.. Sixty newborn infants consisting of 22 with respiratory distress syndrome (RDS), 13 with transient tachypnea of newborn (TTNB), 4 with meconium aspiration syndrome, 10 healthy preterm and 11 healthy full-term infants were included for plasma ET-1 determination. Plasma ET-1 levels were measured by enzyme immunoassay at the of age of 1 day. For those who were diagnosed with RDS, plasma ET-1 concentrations were scheduled for evaluation at the ages of 1, 2, 3, 7, 14, 28, and 35 days as long as oxygen was being used.. On the first day of life, there was no significant difference in plasma ET-1 concentrations between healthy preterm and term infants (3.92 +/- 0.88 vs. 3.56 +/- 1.98 pg/mL, p = 0.606). However, plasma ET-1 concentrations of infants with RDS were significantly higher than those with TTNB (6.46 +/- 0.58 vs. 3.77 +/- 1.29 pg/mL, p < 0.001). In RDS infants, plasma ET-1 concentrations showed no significant difference between those who developed bronchopulmonary dysplasia (BPD, N = 4) and those who recovered (non-BPD, n = 18) (7.84 +/- 1.85 vs. 5.81 +/- 2.76 pg/mL, p = 0.242).. Plasma ET-1 concentrations were similar in preterm and term infants. ET-1 concentrations were higher in infants with RDS than in infants with TTNB, which suggests that plasma ET-1 levels can be useful in the differential diagnosis. However, the plasma ET-1 concentrations can not be a predictor for BPD.

Topics: Birth Weight; Bronchopulmonary Dysplasia; Endothelin-1; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Meconium Aspiration Syndrome; Respiratory Distress Syndrome, Newborn

Topics: Cytokines; Endothelin-1; Humans; Infant, Newborn; Interleukin-6; Prognosis; Respiratory Distress Syndrome, Newborn; Sensitivity and Specificity

We performed serial measurements of plasma endothelin-1 and cytokine levels (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) in 23 children with severe acute respiratory distress syndrome during their first 7 days of disease. We report plasma endothelin-1 and interleukin-6 levels are increased in patients with acute respiratory distress syndrome, and that plasma endothelin-1 levels are significantly greater early in the clinical course of nonsurvivors than survivors. We conclude that plasma endothelin-1 levels are markedly increased in children with severe acute respiratory distress syndrome and speculate that high levels may serve as an early marker of poor outcome.

Topics: Biomarkers; Child, Preschool; Colorado; Endothelin-1; Female; Humans; Infant; Infant, Newborn; Interleukin-1; Interleukin-6; Male; Prognosis; Respiratory Distress Syndrome, Newborn; Statistics, Nonparametric; Survival Analysis; Tumor Necrosis Factor-alpha

To study the relationship between endothelin-1 (ET-1) in the airways and respiratory distress in preterm infants.. ET-1 was determined in 60 tracheal aspirates from 11 preterm intubated infants (gestational age 28.0 +/- 2.5 weeks) during the first week of life.. The concentration of ET-1 of the aspirates was 6 to 2760 pg/mL (median 293 pg/mL). Negative correlations existed between mean log ET-1 and mean airway pressure (R2 = .812) and fraction of inspired oxygen (R2 = .591), whereas a positive correlation was found between the arteriolar/alveolar oxygenation ratio within 3 hours of birth and mean log ET-1 on the first day (R2 = .555).. The association of high ET-1 in the airways with less severe respiratory distress in the early postnatal period may be attributable to effects of ET-1 on surfactant secretion or development of airway epithelium.

Topics: Endothelin-1; Female; Humans; Infant, Newborn; Infant, Premature; Male; Respiratory Distress Syndrome, Newborn; Trachea