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PubMed1994

Meconium analysis to assess fetal exposure to nicotine by active and passive maternal smoking.

We measured nicotine metabolites (cotinine and trans-3'-hydroxycotinine) in meconium of infants of passive or active smokers as a direct marker of fetal exposure to tobacco smoke. Meconium was collected from 55 infants whose mothers were nonsmokers, passive smokers, or light or heavy active smokers. Nicotine metabolite concentration (NMC) in meconium was analyzed by radioimmunoassay and gas chromatography-mass spectrometry. Radioimmunoassay showed the following mean meconium NMCs (in nanograms per milliliter); nonsmoker, 10.9; passive smoker, 31.6; light active smoker; 34.7, and heavy active smoker, 54.6. Analysis of available samples by gas chromatography-mass spectrometry confirmed the presence of cotinine. Correlation between meconium NMC and the degree of maternal smoking was 0.54 (p < 0.001). Meconium NMCs in infants of passive and active smokers were significantly higher than in those of nonsmokers (p < 0.05). Meconium NMC in passive smokers was not significantly different from that in light active smokers (p > 0.05). Thus exposure of the fetus to tobacco smoke is substantial, even by passive maternal smoking. Meconium analysis for nicotine metabolites may be useful for clinical and research purposes.

Cotinine↗
PubMed2001

Nucleated red blood cells in meconium aspiration syndrome.

OBJECTIVE: To evaluate whether the absolute nucleated red blood cell (RBC) count is higher in infants who had meconium aspiration with respiratory symptoms compared with infants with asymptomatic meconium aspiration and controls. METHODS: We compared the absolute nucleated RBC counts during the first 12 hours of life in three groups of term, vaginally delivered infants, including those who had meconium aspiration with respiratory symptoms (n = 11), asymptomatic meconium aspiration (n = 45), and control healthy infants (n = 32). We excluded infants of women with diabetes in pregnancy; hypertension; alcohol, tobacco, or drug abuse; and those with hemolysis, blood loss, or chromosomal anomalies. RESULTS: There were no significant differences among groups in gestational age; gravidity; parity; maternal analgesia; lymphocyte, platelet, and granulocyte counts; and hematocrit. The median nucleated RBC count was significantly higher in the meconium aspiration group with respiratory symptoms (0.007 x 10(9)/L) than the asymptomatic meconium aspiration group (0.004 x 10(9)/L) or controls (0.003 x 10(9)/L). CONCLUSION: At birth, infants with meconium aspiration syndrome had higher absolute nucleated RBC counts compared with infants with asymptomatic meconium aspiration and normal infants.

Adult↗
PubMed2002

Changing obstetric practices associated with decreasing incidence of meconium aspiration syndrome.

OBJECTIVE: To describe changes in neonatal and obstetric practices that may have contributed to the decreasing incidence of meconium aspiration syndrome in our population during this time. METHODS: We compared neonatal and obstetric characteristics of 61 infants diagnosed with meconium aspiration syndrome with 1365 infants born through moderate or thick meconium-stained amniotic fluid at more than 37 weeks' completed gestation. Data were prospectively collected, and all respiratory diagnoses were concurrently made. Three distinct birth year groups were analyzed based on changing obstetric practice paradigms. RESULTS: Meconium aspiration syndrome decreased nearly four-fold from 1990-1992 to 1997-1998 (5.8% to 1.5% of meconium-stained infants more than 37 weeks; P <.003). The only change in neonatal characteristics was a 33% decrease in births more than 41 weeks with a reciprocal 33% increase in births 38-39 weeks during 1997-1998. Significant changes in obstetric practice included more frequent diagnosis of nonreassuring fetal heart rate patterns, greater use of amnioinfusion, and increased cesarean delivery rate in 1997-1998. By logistic regression analysis, the only consistent risk factor for meconium aspiration syndrome across all three epochs was the presence of tracheal meconium. CONCLUSION: Reduction in post-term delivery was the most important factor in reducing meconium aspiration syndrome.

Cesarean Section↗
PubMed1998

Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.

BACKGROUND: Pneumonitis, characterised by large numbers of neutrophils in the lung, is an important feature of the meconium aspiration syndrome. The mechanism underlying the neutrophil influx is not known. We have investigated whether meconium has chemotactic activity and whether such activity is related to the presence of interleukin 8. METHODS: The chemotactic activity of meconium on neutrophils from newborn infants was assessed in a Boyden-chamber assay. Interleukin 8 and formyl-methionyl-leucyl-phenylalanine (f-MLP) served as positive controls. Inhibition of chemotaxis was assessed with monoclonal antibody to interleukin 8. The interleukin-8 concentration was measured by ELISA. FINDINGS: Sterile meconium suspension from seven unrelated newborn babies increased migration of neutrophils from neonates in comparison with random migration (79, 72, 70, 50, 58, 88 microm vs 46 microm; p<0.001). This effect was greatest at a meconium concentration of 5 g/L, although differences between samples from individual babies were observed. Interleukin 8 was present in all meconium suspensions (480-3980 ng/L). Anti-interleukin-8 inhibited neutrophil migration. INTERPRETATION: Interleukin 8 is present in meconium and it induces chemotaxis of neutrophils in vitro. This mechanism may have a role in the pathogenesis of pneumonitis in meconium aspiration syndrome.

Chemotaxis, Leukocyte↗
PubMed2002

The effect of meconium staining of amniotic fluid on the growth of Escherichia coli and group B streptococcus.

OBJECTIVE: To compare the effect of meconium staining on the growth rate of Escherichia coli and group B streptococci (GBS) in amniotic fluid. STUDY DESIGN: Sterile meconium was added in different concentrations to pooled sterile amniotic fluid obtained from term mothers. Meconium concentration was equal to: 1, 1.5, 3, 6, and 12 mg meconium/ml amniotic fluid. Amniotic fluid was quantitatively inoculated with E. coli and GBS type II and type III organisms (10(3) organisms/ml). Clear amniotic fluid and Todd-Hewitt broth served as controls. Growth rates of organisms were measured at 2, 4, 6, 8, and 24 hours after inoculation. RESULTS: Clear amniotic fluid was completely inhibitory for growth of E. coli even after 24 hours of incubation. In contrast, after 6 hours of incubation, significantly increased growth of GBS occurred (10(5) organisms/ml) (p<0.0001). The inhibitory effect on E. coli was observed even with meconium concentration of up to 1.5 mg/ml. In contrast, even the smallest concentration of meconium (1 mg/ml) resulted in a 2-log fold increase of GBS within 4 hours. The more rapid growth rate of GBS compared to E. coli persisted even at moderate staining of amniotic fluid (6 mg/ml) in the first 8 hours of incubation (p<0.005). In the presence of thick meconium (12 mg/ml), during the first 6 hours of incubation, the growth rates of GBS and E. coli were nearly similar. CONCLUSIONS: GBS (type II and III) growth, in contrast to E. coli, was less inhibited by amniotic fluid, occurred at a more rapid rate, and was enhanced at lower concentrations of meconium. As such, the presence of even light meconium staining in cases of rupture of membranes of even less than 6 hours in a mother who is a GBS carrier should be considered as a risk factor for the development of perinatal GBS infection.

Amniotic Fluid↗
PubMed2002

In utero meconium exposure increases spinal cord necrosis in a rat model of myelomeningocele.

BACKGROUND/PURPOSE: The rationale for in utero repair of myelomeningocele has been supported experimentally by the observation of preserved neural function after prenatal closure of surgically created defects compared with nonrepaired controls. The mechanism of injury to the exposed neural elements is unknown. Postulated mechanisms include trauma to the herniated neural elements or progressive injury from amniotic fluid exposure as gestation proceeds. A component of amniotic fluid that may contribute to neural injury is meconium. In the current study the effect of human meconium on the exposed spinal cord in a fetal rat model of myelomeningocele was examined. METHODS: Twenty time-dated pregnant rats underwent laparotomy at 181/2 days of gestation. The exposed uterus was bathed in ritrodrine for tocolysis. The amniotic cavity was opened over the dorsal midline of the fetal rat, and, under a dissecting microscope (x25), a 2- to 3-level laminectomy was performed. Under magnification (x40), the translucent dura was opened using a 25-gauge needle as a knife. Two fetuses per dam were operated on. In the control group, the amniotic fluid was restored with saline solution, whereas in the experimental group a solution of Human meconium diluted (10%) in saline was used to restore the amniotic fluid. Fetuses were harvested by cesarean section at 211/2 days' gestational age. The liveborn pups were then killed and fixed in 10% formaline. Sections 10 micrometer thick were stained with H&E and studied by light microscopy for evidence of spinal cord injury. RESULTS: Seven of 20 (35%) experimental rat pups and 6 of 20 (30%) control rat pups were liveborn. All liveborn pups had severe paralysis of the hindlimbs and tail, so that functional differences between the 2 groups could not be detected. Histologic examination of 13 spinal cords at the site of surgical exposure showed that necrosis of neural tissue in 5 of 7 meconium-exposed rat pups was increased when compared with that observed in the 6 fetuses exposed to amniotic fluid without meconium. In general, inflammation was greater and repair processes appeared delayed in meconium-exposed rat pups. CONCLUSIONS: Exposure of the spinal cord of fetal rats to amniotic fluid by surgically created myelomeningocele leads to severe functional impairment. Histologically recognizable necrosis of neural elements was increased in those animals that were exposed to diluted human meconium in the amniotic fluid. The results support the hypothesis that meconium may contribute to the pathophysiology of spinal cord injury observed in myelomeningocele.

Amniotic Fluid↗
PubMed1993

Acid-base significance of meconium discovered prior to labor.

Although the significance of meconium in the amniotic fluid diagnosed during labor remains problematic, there is little information regarding the significance of meconium discovered prior to labor. The present study consisted of 40 term pregnancies with meconium found at amniocentesis for lung maturity (n = 7) or elective cesarean section (n = 33) and 40 uncomplicated, control pregnancies with clear amniotic fluid at elective cesarean section. The mean umbilical artery (UA) blood pH was 7.26 in the meconium group and 7.28 in the control group. Overall, the frequency of fetal acidemia (UA pH < 7.20) was 15% (6 of 40) of the infants in the meconium group versus 8% (3 of 40) in the control group (p = 0.24). All nine of these infants had a respiratory acidosis defined as a UA blood pH less than 7.20 with normal bicarbonate and elevated carbon dioxide pressure. Importantly, none of the neonates had metabolic acidemia and all had uncomplicated hospital courses. All of the pregnancies reported were promptly delivered because of meconium and we therefore cannot recommend nonintervention when meconium is diagnosed in the antepartum period. Meconium discovered prior to labor is not necessarily a marker of immediate or chronic fetal compromise.

Acid-Base Equilibrium↗
PubMed2000

Dextran reduces surfactant inhibition by meconium.

We have previously shown that an addition of dextran to surfactant increases resistance to inactivation by albumin. The present study was designed to investigate whether dextran has a protective effect against inactivation of surfactant by meconium. The dynamic surface properties of various mixtures of modified natural surfactant (Curosurf), meconium and dextran were evaluated with the pulsating bubble technique. In the absence of meconium, an addition of dextran at 10 mg ml(-1) significantly shortened the surface adsorption time of Curosurf suspended in normal saline at a concentration of 5 mg ml(-1) from 1.6+/-1.3 (mean +/- SD) sec to 0.4+/-0.4 sec (p < 0.05). Meconium at 5 mg ml(-1) increased the mean minimum surface tension (gammamin) after 3 min of pulsation from 2.1 mN m(-1) to 24 mN m(-1) (p < 0.05). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture significantly reduced the gammamin to 6.4+/-4.5 mN m(-1) and 2.6+/-5.6 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). Meconium also increased the maximum surface tension (gammamax) of Curosurf from about 33 mN m(-1) to 53 mN m(-1). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture reduced the gammamax to 41 and 39 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). There were significant negative correlations between dextran concentration and both gammamin and gammamax. We conclude that dextran reduces surfactant inhibition by meconium in a dose-dependent manner.

Adsorption↗
PubMed2006

Trypsin and antitrypsin activities and protein concentration in serial meconium and feces of healthy newborns.

BACKGROUND: Meconium has the potential for being the matrix on which markers of fetal exposure to physiologic and non-physiologic agents during intrauterine life can be analyzed. The aim of this study was to compare trypsin and antitrypsin activities and protein concentration during intra- and extrauterine human development based on an assessment of these parameters in serial meconium and first feces of healthy, term newborns during the first four days of life. METHODS: One hundred and eighteen mature, term newborns were studied. Single portions of meconium or feces were taken prospectively from day 1 to day 4. In ten newborns each meconium and feces passed by the infant from birth up to the fourth day after delivery was collected individually. Trypsin activity was measured using L-TAPA (N-alpha-tosyl-l-arginine-p-nitroanilide) as substrate, trypsin inhibitory capacity (TIC) with N-alpha-benzoyl-dl-arginine-p-nitroanilide (BAPNA) as substrate, and protein concentration by the method of Lowry et al. RESULTS: Meconium and feces of healthy newborns demonstrated a decrease in TIC during the first two days of life and an increase in trypsin activity over the first three successive days of life. No correlation was observed between the variability of both parameters. During the first three days of a newborn's life, significant correlation was observed between TIC and protein concentration in meconium and first feces. In the course of proteolytic activity changes in successive portions of meconium and feces, a transient peak occurs on the 2nd-4th day of life. CONCLUSIONS: The gradual decrease in protease inhibitor activity and low trypsin activity in successive portions of meconium from the first two days of extrauterine life may provide a retrograde chronological depiction of the course of the second and third trimesters of intrauterine life. Serial collection of feces over 2-4 days may provide a reflection of the dynamics of the postnatal increase in the newborn's pancreatic exocrine functions.

Analysis of Variance↗
PubMed1987

Excretion of cobalamin and haptocorrin in the meconium of cystic fibrosis, premature, and control neonates.

Excretion of haptocorrin (R binder), cobalamin, and other corrinoids was studied in meconium from cystic fibrosis (n = 4), premature (n = 3), and control neonates (n = 13). Corrinoids content was 1.67 +/- 0.92 pmol/mg protein in meconium of cystic fibrosis (CF) neonates but only 0.33 +/- 0.37 and 0.48 +/- 0.47 pmol/mg protein, respectively, in that of prematures and controls. Considering its molecular mass (110,100 +/- 10,100) and its mean isoelectric point (3.67 +/- 0.20), haptocorrin remained undergraded in the meconium of CF neonates whereas it was partially degraded in the meconium of prematures and in most of the meconium from controls. Sequestration of cobalamin by undergraded haptocorrin can explain its increased excretion in CF meconium. Cobalamin-binding capacity of haptocorrin was 22.13 +/- 15.50 pmol/mg protein in CF meconium and about 400-fold lower in meconium of prematures and controls. This may correspond to a fetal intestinal hypersecretion in cases of CF.

Cystic Fibrosis↗
PubMedDate not supplied

Analysis of methadone and its primary metabolite in meconium.

Methods for analysis of methadone and its principal metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in meconium, based on fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC) and diode array detection were developed. Meconium and urine samples of 16 neonates from 15 methadone-using mothers were analyzed. Because of the lower detection limit and the possibility of coanalyzing EDDP, meconium analysis with HPLC for detecting methadone use is very much preferable to FPIA. Identical results were obtained with HPLC analysis for both matrices: methadone or EDDP or both could be detected in the urine and meconium samples from 15 children. The amount of EDDP in meconium was much higher than the amount of methadone (ratio, 9.6). EDDP only was detected in eight of the meconium samples. A positive correlation was found between the methadone dose of the mothers and the methadone concentration in meconium, but not with the EDDP concentration in meconium.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

delta 9-THC metabolites in meconium: identification of 11-OH-delta 9-THC, 8 beta,11-diOH-delta 9-THC, and 11-nor-delta 9-THC-9-COOH as major metabolites of delta 9-THC.

Gas chromatography-mass spectrometry (GC-MS) analysis of meconium specimens screening positive for cannabinoids by the EMIT 20 Assay showed a low confirmation rate for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). A study was designed to investigate the possible contribution of other delta 9-tetrahydrocannabinol (THC) metabolites, including glucuronides, to the overall response of the EIA. delta 9-THC-glucuronide was synthesized in order to develop the most efficient procedure for hydrolysis of glucuronides in meconium. Procedures were developed for the extraction and GC-MS analysis of delta 9-THC, 11-OH-delta 9-THC, 8 alpha- and 8 beta-OH-delta 9-THC, 8 beta,11-diOH-delta 9-THC, and THCCOOH, after enzymatic hydrolysis of meconium extracts. It is concluded that enzymatic hydrolysis of meconium extracts is necessary for efficient recovery of delta 9-THC metabolites; delta 9-THC and its 8-OH metabolite(s) are basically absent in meconium specimens; and 11-OH-delta 9-THC and 8 beta,11-diOH-delta 9-THC contribute significantly to the immunoassay response of meconium extracts. Analysis of several meconium specimens that screened positive for cannabinoids but failed to confirm for THCCOOH showed significant amounts of 11-OH-delta 9-THC and 8 beta,11-diOH-delta 9-THC. Therefore, GC-MS confirmation of cannabinoids in meconium should include analysis for these two metabolites in addition to THCCOOH.

Dronabinol↗
PubMed2006

Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?

BACKGROUND: Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect. METHODS: Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use. RESULTS: A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p = 0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001). CONCLUSION: We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.

Adult↗
PubMed2003

Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse.

BACKGROUND: Meconium and hair are two biological markers of in utero exposure to illicit drugs. OBJECTIVE: To compare the sensitivity of the two tests for different drugs. SETTING: Motherisk laboratory which tests in utero drug exposure in Toronto. METHODS: Cocaine, benzoylecgonine, opiates, cannabis, benzodiazepines, methadone, and barbiturates were measured in pairs of hair and meconium samples from the same neonates. RESULTS: Meconium was marginally more sensitive than neonatal hair for detection of cocaine and cannabis, possibly because it may detect second trimester exposure whereas hair grows only during the third trimester of pregnancy. There was a significant correlation between hair and meconium concentrations of cocaine, cannabis, and opiates. CONCLUSION: In cases of clinical suspicion and a negative neonatal urine test, both meconium and hair are effective biological markers of in utero illicit drug exposure. Meconium may be more sensitive, but neonatal hair is available for three months whereas meconium is available for only one or two days. In contrast, the use of meconium, being a discarded material, is more acceptable to some parents than hair testing, which entails cutting scalp hair from the newborn.

Cannabis↗
PubMed1980

Sequential effects of acute meconium obstruction on pulmonary function.

The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1--2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.

Airway Obstruction↗
PubMed1992

Surfactant lavage in a piglet model of meconium aspiration syndrome.

Meconium aspiration continues to be a major cause of morbidity and mortality in newborn infants and is one of the most common indications for extracorporeal membrane oxygenation. Lab studies have suggested that meconium inactivates surfactant and displaces surfactant from the alveolar surface. A recent report has suggested a clinical role for surfactant therapy in human infants with meconium aspiration. We evaluated the effect of surfactant (Survanta) lavage on a piglet model of meconium aspiration. Meconium pneumonitis was created by administration of 4 mL/kg of a 20% slurry of human meconium via endotracheal tube. Twenty-four newborn piglets were then randomly assigned to one of three groups: 1) suction only (n = 7), 2) saline lavage (n = 5), or 3) surfactant lavage (n = 7). Five piglets were excluded from analysis due to death from pneumothorax during meconium administration (n = 3), death from pneumothorax during saline lavage (n = 1), and death from pneumothorax during surfactant lavage (n = 1). The surfactant group had a statistically significant (p less than 0.05) improvement in arterial to alveolar oxygen ratio gradient versus both control groups for the first 3 h. The oxygenation index was statistically significant versus the suction only group at 1, 3, and 4 h. Surfactant lavage of meconium aspiration in piglets results in short-term improvement of oxygenation and warrants further study.

Animals↗
PubMed1996

Direct effects of meconium on rat tracheal smooth muscle tension in vitro.

Increased airway resistance is a component of the meconium aspiration syndrome. Experiments were done to determine whether meconium can have a direct affect on tracheal smooth muscle tension. Tracheal segments (4-5 mm long) were isolated from male Sprague-Dawley rats and suspended in organ baths with physiologic salt solution at 37 degrees C gassed with 95% O2-5% CO2. Each segment was attached to a fixed glass rod on one side and to a force displacement transducer on the other side to measure transverse tension. The segments were stretched to 1.5 g of tension and equilibrated for 2-5 h. Human meconium was diluted in physiologic salt solution (20 g/100 mL) and filtered through gauze. Tension was generated in the segments by adding acetylcholine (10(-6) M) to the tissue bath. Addition of meconium to the organ bath (0.1-5 mg/mL) caused tracheal smooth muscle relaxation in 44% of tracheal segments tested. Contraction occurred in 8% of tested segments, but only at the intermediate and low doses. The amount of relaxation increased significantly in a concentration-dependent manner. These responses were not affected by pretreating segments with indomethacin, removing the tracheal epithelium, using KCl to generate tone, or by heating meconium above 60 degrees C for 1 h. Addition of oleic acid to the organ bath (3.5 x 10(-6) to 3.5 x 10(-4) M) caused concentration-dependent tracheal smooth muscle responses (with relaxation predominating at 3.5 x 10(-4) M and contraction predominating at 3.5 x 10(-6) M). These results suggest that meconium can cause tracheal smooth muscle relaxation by a mechanism that does not appear to be mediated by cyclooxygenase products, by the tracheal epithelium, or a protein. The direct action of meconium on tracheal smooth muscle, which may in part be mediated by a fatty acid, does not appear to contribute significantly to the increased airway tone associated with the meconium aspiration syndrome.

Acetylcholine↗
PubMed2003

Meconium aspiration stimulates cyclooxygenase-2 and nitric oxide synthase-2 expression in rat lungs.

To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide, we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase-1 (COX-1) and -2 (COX-2) and endothelial (NOS-3) and inducible (NOS-2) nitric oxide synthase in rat lungs. Anesthetized, tracheotomized, and ventilated rats received 3 mL/kg human meconium suspension intratracheally (n = 19), and 14 control rats received an equal volume of saline. Ten rats were pretreated with indomethacin, and 13 rats were pretreated with dexamethasone. The lungs were ventilated with 70% oxygen for 3 h after the insult, and the level of COX-1, COX-2, NOS-2, and NOS-3 mRNA in lung tissue was analyzed by Northern blot hybridization. Furthermore, the expression and localization of the enzyme proteins was analyzed by immunohistochemistry. COX-1 and NOS-3 were clearly expressed in the lungs of control rats, whereas the level of COX-2 and NOS-2 expression was minimal. Meconium administration did not affect the expression of COX-1, but COX-2 expression was up-regulated in the respiratory epithelium and alveolar macrophages. Meconium also induced up-regulation of NOS-2 in the pulmonary epithelium, vascular endothelium, and macrophages. Indomethacin pretreatment did not affect the enzyme expressions, whereas dexamethasone administration significantly inhibited the meconium-induced COX-2 and NOS-2 up-regulation. Our data thus indicate that intrapulmonary meconium up-regulates lung COX-2 and NOS-2 gene expression, suggesting an important role for prostaglandins and nitric oxide in the meconium aspiration-induced pulmonary inflammation and hemodynamic changes.

Age Factors↗