endothelin-1 and Meconium-Aspiration-Syndrome

Plasma endothelin 1 concentrations were determined in infants with meconium stained amniotic fluid. Plasma endothelin 1 concentration in the study group (5.23 pg/ml) was statistically higher than that in the control group (1.12 pg/ml). Cord blood pH and base excess values were significantly lower in infants with meconium stained amniotic fluid when compared with the control group. There was no correlation between endothelin 1 concentrations and pH or base excess values. Results suggest that meconium passage is not a physiological event, even if meconium stained infants appear to be clinically healthy.

Topics: Amniotic Fluid; Analysis of Variance; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Fetal Blood; Gestational Age; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) disrupts perinatal decreases in pulmonary vascular resistance (PVR) and is the commonest cause of neonatal pulmonary hypertension. The contribution of the potent vasoactive agent urotensin-II (U-II), in the pathophysiology of this condition, is unknown. In a new perinatal model of MAS, we combined measurement of circulating U-II levels with U-II receptor blockade studies. Nineteen anesthetized lambs were instrumented then randomly allocated to the following groups: 1) control (n = 5), 2) control plus specific U-II receptor blockade with palosuran (n = 5), 3) tracheal instillation of meconium (n = 5), 4) meconium instillation plus palosuran (n = 4). Hemodynamics, PVR, and plasma U-II were measured for 6 h after delivery. After birth in controls, U-II increased (p < 0.05), and PVR fell (p = 0.01) and this fall was prevented by U-II receptor blockade. By contrast, meconium lambs displayed a greater rise in U-II levels (p < 0.05 versus control) with an increase in PVR (p < 0.005) that was attenuated by U-II receptor blockade (p < 0.001). These findings suggest that U-II normally acts as a pulmonary vasodilator after birth, but in the presence of MAS, it assumes a vasoconstrictor role. U-II receptor blockade also improves pulmonary hemodynamics in this model.

Topics: Animals; Animals, Newborn; Blood Pressure; Cardiac Output; Disease Models, Animal; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Infant, Newborn; Meconium Aspiration Syndrome; Oxygen; Pulmonary Artery; Quinolines; Receptors, G-Protein-Coupled; Sheep; Time Factors; Up-Regulation; Urea; Urotensins; Vascular Resistance; Vasoconstriction; Vasodilation

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

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

In order to test the hypothesis that endothelin-1 (ET-1) directly contributes to the pathophysiology of pulmonary hypertension induced by meconium aspiration, we randomized 12 anesthetized and paralyzed piglets to receive BQ-123, a selective endothelin-A receptor antagonist (BQ group), or normal saline (NS group) after meconium aspiration. The animals were instilled with meconium mixture (3 mL/kg) via an endotracheal tube, and then given intravenous BQ-123 (2 mg/hr) or normal saline. Plasma ET-1 concentrations, arterial blood gases, and hemodynamics were measured at baseline and at 60, 120, 180, and 240 minutes after instillation. The results showed that plasma ET-1 concentrations were similar in both groups. However, in the BQ group, pulmonary artery pressure was significantly lower after 120 minutes (p < 0.05 at 120 min, p < 0.01 at 180 and 240 min) and pulmonary vascular resistance was significantly lower after 180 minutes (p < 0.01) than in the NS group. No significant difference was found in systemic hemodynamics. These data suggest that ET-1 directly contributes to the pathophysiology of pulmonary hypertension induced by meconium aspiration.

Topics: Animals; Animals, Newborn; Endothelin Receptor Antagonists; Endothelin-1; Hemodynamics; Humans; Hypertension, Pulmonary; Infant, Newborn; Meconium Aspiration Syndrome; Peptides, Cyclic; Swine

Sequential changes in plasma endothelin-1 (ET-1) and pulmonary hemodynamics were studied in a piglet model of meconium aspiration syndrome (MAS). Sixteen piglets were randomly divided into meconium (MEC) and normal saline (NS) groups (8 animals/group). The animals of the MEC group were instilled with meconium (20% in normal saline) via an endotracheal tube (3 ml/kg), and the animals of the NS group instilled with the same amount of normal saline. The plasma ET-1 as well as pulmonary mechanics, arterial blood gas and hemodynamics were measured at baseline and 60, 120, 180 and 240 min after instillation. The results showed that plasma ET-1 level of the MEC group was significantly higher after meconium aspiration as compared with NS group (p < 0.05 at 60 and 120 min, p < 0.01 at 180 and 240 min). Furthermore, pulmonary vascular resistance (PVR) increased and remained elevated after 120 min (p < 0.01) and pulmonary artery pressure (PAP) increased after 180 min (p < 0.01). The correlation was significant between ET-1 and PVR (r = 0.92, p < 0.001) as well as ET-1 and PAP (r = 0.89, p < 0.001). These data suggest that elevation of ET-1, which has long-lasting vasoconstriction effect, may play an important role of pulmonary hypertension of MAS.

Topics: Animals; Animals, Newborn; Blood Pressure; Disease Models, Animal; Endothelin-1; Hemodynamics; Humans; Infant, Newborn; Lung; Meconium Aspiration Syndrome; Swine

To evaluate the role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in the development of meconium aspiration-induced pulmonary hypertension, plasma ET-1 and ANP levels were measured serially for 6h after meconium instillation in juvenile pigs. Eleven 10-week-old, anaesthetized and catheterized pigs received intratracheally a bolus of 3 ml kg(-1) 20% human meconium, and five of them were premedicated with 30 mg kg(-1) methylprednisolone i.v. Another six pigs served as controls and were given 3 ml kg(-1) sterile saline intratracheally. Meconium instillation resulted in an increase in plasma ET-1 levels with a significant correlation to the simultaneously increasing PVR (r = 0.72). Methylprednisolone had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the second phase (1-6 h) rise with a concomitant attenuation of the progressive pulmonary hypertension. ANP concentrations were higher in the meconium than in the control group throughout the study and further increased after steroid treatment with a good correlation to ET-1 (r = 0.86). Thus, the postinjury rise in circulating vasoactive peptides, together with the pulmonary hypertensive response, and modulation of the peptide balance and pressor reaction by steroids, suggest a contributory role for ET-1 and ANP in the development of pulmonary hypertension after meconium aspiration.

Topics: Animals; Anti-Inflammatory Agents; Atrial Natriuretic Factor; Endothelin-1; Humans; Hypertension, Pulmonary; Infant, Newborn; Meconium Aspiration Syndrome; Methylprednisolone; Swine