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Angiotensin II receptor blockade inhibits pneumocyte apoptosis in experimental meconium aspiration.

Lung tissue inflammation and apoptosis are implicated in the pathogenesis of meconium aspiration-induced lung injury in the newborn, but the mechanisms of these reactions are still poorly known. We investigated the time-dependent leukocyte influx and appearance of apoptosis, as well as the contribution of angiotensin (ANG) II receptor action on these processes in the meconium-induced lung injury. Experimental meconium aspiration was induced by intratracheal instillation of human meconium in 18 rats, and eight rats were further pretreated with an unspecific ANG II receptor inhibitor saralasin. Rats were ventilated with 60% oxygen for 1, 3, or 5 h, and the lungs were then studied histologically for tissue injury and with DNA nick-end labeling and electron microscopy for apoptotic cell death. Lung tissue myeloperoxidase activity and expression of angiotensinogen mRNA and endothelial monocyte-activating polypeptide (EMAP) II protein were also analyzed. The meconium-instilled lungs showed increasing neutrophil migration and histologic injury after the first hour, whereas the number of epithelial apoptotic cells was elevated from the control level throughout the study. Myeloperoxidase activity was high, and the angiotensinogen mRNA and EMAP II protein was up-regulated at 5 h after the meconium insult. Pretreatment with saralasin significantly prevented the increase in lung tissue myeloperoxidase activity, EMAP II, and lung epithelial apoptosis. The results suggest that pulmonary meconium insult rapidly results in epithelial apoptosis, before significant neutrophil sequestration into the lungs. Apoptotic cell death is further connected with ANG II receptor action in the meconium-contaminated lung tissue.

Angiotensin Receptor Antagonists↗

Pentoxifylline reduces regional inflammatory and ventilatory disturbances in meconium-exposed piglet lungs.

Neonatal meconium aspiration frequently produces severe respiratory distress, which is associated with patchy pulmonary neutrophil influx and inflammatory injury. To examine the effects of pentoxifylline (PTX), a potent anti-inflammatory agent, on regional pulmonary inflammation and ventilation after meconium aspiration, we studied 17 anesthetized and ventilated neonatal piglets (age <2 d) for 12 h. After unilateral intrapulmonary instillation of meconium, PTX treatment was started in nine animals, and eight untreated animals served as controls. Bronchoalveolar lavage (BAL) fluid and lung tissue were studied for inflammatory variables at the end of the study, and changes in regional ventilation were serially analyzed with a dynamic pulmonary x-ray imaging method. Meconium insufflation increased BAL fluid total cell, neutrophil, and macrophage counts and tumor necrosis factor-alpha (TNF-alpha) and protein concentrations as well as lung tissue myeloperoxidase activity in the instilled lungs, compared with the noninstilled side. PTX treatment prevented the increase of BAL fluid alveolar macrophage count and TNF-alpha and protein concentrations in the meconium-instilled lungs but had no significant effect on the pulmonary neutrophil accumulation. Ventilation of the meconium-insulted lung was initially disturbed similarly in both study groups, but PTX administration prevented the sustained local ventilatory perturbation at 4, 6, and 12 h after meconium instillation. The results thus indicate that PTX treatment may attenuate meconium-induced regional ventilation derangements, mainly through its effects on local alveolar macrophages and TNF-alpha production as well as alveolocapillary permeability rather than via significant prevention of accumulation of active neutrophils in the insulted lungs.

Animals↗

Pancreatic phospholipase A2 contributes to lung injury in experimental meconium aspiration.

To investigate the role of pancreatic (group I) secretory PLA2 (sPLA2-I) in the pathogenesis of meconium aspiration syndrome, human particulate meconium or its supernatant either before or after extraction of PLA2-I was insufflated into rat lungs. In addition, the pulmonary effects of intra-tracheal human and bovine PLA2-I were studied. Lungs with saline instillation served as controls. Intrapulmonary particulate meconium (both before and after PLA2-I extraction), unlike meconium supernatant, resulted in markedly elevated lung tissue PLA2 catalytic activity and human PLA2-I concentrations when compared with controls. On the other hand, tissue concentrations of the group II PLA2 remained unchanged in all meconium lungs. Pulmonary PLA2-I concentrations further correlated positively with lung injury scores. Instillation of meconium-derived human PLA2-I, at a concentration of one-third of that in particulate meconium, did not raise PLA2 activity or concentrations of PLA2-I or PLA2-II in the lung tissue from the control level, but still resulted in significantly elevated lung wet/dry ratio and injury score. In contrast, insufflation of bovine pancreatic PLA2 increased the lung tissue enzyme activity and wet/dry ratio from the control level, but had no effect on the type II PLA2 concentration or lung injury score. Our data thus indicate that human pancreatic PLA2, introduced in high amounts within aspirated meconium especially in particulate form, is a potent inducer of lung tissue inflammatory injury.

Animals↗

Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration.

OBJECTIVE: Meconium aspiration syndrome remains a common cause of respiratory failure in neonates. The acute effects of meconium aspiration are inactivation of lung surfactant in vivo and in vitro. This study investigated the delayed effects of meconium on alveolar surfactant phospholipids and protein levels in spontaneously breathing animals. METHODS: Twenty-two adult rats were given 4.3 mg of dry weight human meconium after endotracheal intubation. Rats were briefly mechanically ventilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6), 48 (n = 6), and 72 hours (n = 4). Control animals received the same volume of normal saline (n = 7) or no meconium (n = 7). Bronchoalveolar lavage and tissue specimens were evaluated for inflammatory cells, total proteins, surfactant phospholipids, and surfactant proteins. RESULTS: Meconium caused exudative lung injury that was reflected in increased cell counts and proteins in alveolar lavage fluid. The peak injury occurred at 16 hours after instillation, whereas recovery occurred by 72 hours. Although total lavage fluid phospholipids did not change over time, phospholipid and dipalmitoyl phosphatidylcholine in large aggregates tended to decrease at 24 hours. Western blot analysis demonstrated time-dependent qualitative decreases in surfactant proteins A and B (SP-A, SP-B) in meconium-instilled animals compared with the controls. ELISA for SP-B confirmed the Western blot findings with total SP-B in large aggregate decreasing from 25 +/- 4 microg in controls to 6.6 +/- 0.8 microg at 24 hours of injury. CONCLUSIONS: Our study suggests that the exudative lung injury with meconium instillation is associated with decreased levels of SP-A and SP-B in the large aggregate fraction of lung surfactant. We speculate that decreased secretion and/or increased degradation accounts for lower levels of SP-B in bronchoalveolar lavage fluid.

Animals↗

Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn.

OBJECTIVE: The objective of this study was to detect fetal exposure to nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to determine the relationship between fetal exposure to NSAIDs and the development of persistent pulmonary hypertension of the newborn (PPHN). METHODS: In a case-control study of the inborn and outborn nurseries of a large urban medical center, meconium was collected from 101 newborn infants (40 with the diagnosis of PPHN based on clinical or echocardiographic criteria and 61 randomly selected, healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas chromatography/mass spectrometry. The risk of developing PPHN was determined in infants who were exposed antenatally to NSAID. RESULTS: Infants with PPHN (n = 40) had a mean gestation of 38.9 weeks and birth weight of 3524 g, which were similar to the those of the control group (n = 61). However, the incidence of low Apgar scores (</=6) at 1 minute and 5 minutes was significantly higher in the PPHN group than in the control group. The diagnoses associated with PPHN were primary PPHN (25%), meconium aspiration syndrome (35%), respiratory distress syndrome (20%), low Apgar score/asphyxia (12.5%), and pneumonia/sepsis (8%). Mean duration of ventilator support for the PPHN group was 11 days. Nitric oxide (NO) was given to 19 infants (47.5%) for a mean duration of 25.4 hours. Fourteen of the 19 infants who were treated with NO (74%) required extracorporeal membrane oxygenation, and 2 died. The overall incidence of positive NSAID in meconium in the study population (n = 101) was 49.5%: 22.8% were positive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and 43.6% for aspirin. There was poor agreement (Cohen's kappa = 0.09) between maternal history of NSAID use and NSAID detection in meconium. PPHN was significantly associated with 1) the presence of at least 1 NSAID in meconium (odds ratio [OR] = 21.47; 95% confidence interval [CI] = 7.12-64.71) or 2) the presence in meconium of aspirin (OR = 8.09; 95% CI = 3.27-20.10), ibuprofen (OR = 12.89; 95% CI 3.93-42.32), or naproxen (OR = 3.31; 95% CI = 1.17-9.33). By logistic regression analysis, low Apgar scores at 1 and 5 minutes and the antenatal exposure to aspirin, naproxen, and ibuprofen were significantly associated with PPHN and treatment with inhaled NO or extracorporeal membrane oxygenation. CONCLUSION: We confirm by meconium analysis the results of previous studies that demonstrated that the use of NSAIDs during pregnancy, particularly aspirin, ibuprofen, and naproxen, is high; is grossly underestimated by maternal history; and is significantly associated with PPHN. Thus, the easy access to over-the-counter NSAIDs of pregnant women should be reevaluated, and the potential dangers of these drugs to the newborn infant should be more effectively promoted.

Anti-Inflammatory Agents, Non-Steroidal↗

The placenta in meconium staining: lesions and early neonatal outcome.

PURPOSE: To evaluate the immediate neonatal outcome and the presence of various placental lesions in 96 pregnancies with meconium-stained amniotic fluid. MATERIALS AND METHODS: The patients were divided into a group with acute (N = 41) and subacute and chronic (N = 55) meconium staining of the placenta. Apgar scores, arterial cord pH and admission to the neonatal intensive care unit (NICU) were determined in addition to the findings on gross and microscopic examination of the placentas. RESULTS: Of the 53 live births with subacute and chronic meconium staining, 13% had Apgar Scores < or = 7 at 5 minutes compared to 7% with acute meconium staining. Similarly, a significantly lower umbilical artery pH was determined in the former group [(32%) versus (7%)], (p < 0.01). When 9 different pathologic lesions of the placenta were evaluated microscopically, the frequency of villous vascular thrombosis (25.4%), infarcts (38%), acute chorioamnionitis (20%), villous edema (9.1%) and villitis (14.5%) was significantly higher in the group with longer meconium exposure compared to the other group (2.4%), (9.7%), (7.3%), (0%), and 1 (2.4%), respectively. In addition, when tested for 4 different lesions, cases with acute meconium were less likely to have one or more lesions. When one or more placental lesions were found, NICU admission rate was significantly higher in the patients with subacute and chronic meconium. CONCLUSION: Subacute and chronic meconium discharge is associated with significant placental lesions and an increased risk of adverse pregnancy outcome in the immediate neonatal period.

Acidosis↗

[Meconium aspiration syndrome. 1. Perinatal problems; etiology and types].

Obstetric literature deals with meconium stained amniotic fluid (AF) in various ways when judging it as an indicator of fetal distress. This evidently reflects the difficulty of finding overt relations between measurable alterations in the condition of the fetus or of the newborn infant and the amount of meconium passed into the AF. Nor is the moment predictable by means of fetal monitoring when meconium is passed. Discussing these problems in the light of the consecutive course of events resulting finally in meconium aspiration some of the discrepancies can be explained without difficulty. Considering also the kinetics of formation and excretion of AF the distinction of 3 variants of meconium aspiration syndrome is possible: 1. late meconium aspiration syndrome in non-asphyctic infants, 2. late meconium aspiration syndrome in asphyctic infants, 3. "connatal" meconium aspiration syndrome.

Amniotic Fluid↗

Correlation of meconium-stained amniotic fluid, early intrapartum fetal pH, and Apgar scores as predictors of perinatal outcome.

A prospective study was undertaken to determine if the passage of meconium during the early intrapartum period (cervical dilatation 3 cm or less), the type of meconium passed (thick versus thin), and fetal pH values could be correlated with Apgar scores as a predictor of neonatal outcome. One hundred seventy-seven patients had meconium-stained amniotic fluid and a cervical dilatation of 3 cm or less at admission. Group 2 (thick meconium) had significantly lower 1- and 5-minute Apgar scores, lower scalp pH values, and increased risk factors, such as prolonged pregnancy, small-for-gestational-age fetus, and fetal heart rate abnormalities. Group 2 (thin meconium) and the control group (nonmeconium) appeared to have no increased associated risks. Thick meconium as a single variable appeared to be the most significant factor influencing fetal outcome; however, if an associated fetal heart rate abnormality was present, perinatal morbidity was greatly increased as indicated by fetal acidosis and lower 1- and 5-minute Apgar scores. It thus appears that early passage of thick meconium does correlate with fetal outcome and increased perinatal morbidity. The significance of meconium passage is discussed and a modern obstetric management scheme for these high-risk patients is presented.

Acidosis↗

Meconium-stained amniotic fluid. Current controversies.

Meconium-stained amniotic fluid is commonly found in obstetrics: it occurs in 9-20% of deliveries. Meconium passage into the amniotic fluid may be an antepartum or intrapartum event. Meconium aspiration may occur antepartum or intrapartum or at the infant's first breath. The prognosis in neonates with meconium aspiration syndrome appears to be related to antepartum hypoxemic damage to the lungs. This paper covers the pathophysiology of meconium aspiration and meconium aspiration syndrome, treatment options to prevent meconium aspiration and practical information on assessing fetal heart rate tracings. The necessity of tracheal suctioning in all neonates with meconium-stained amniotic fluid is controversial.

Amniotic Fluid↗

Use of maternal plasma level of zinc-coproporphyrin in the prediction of intrauterine passage of meconium: a pilot study.

OBJECTIVE: To evaluate the usefulness of maternal plasma zinc-coproporphyrin (ZCP) level as a marker for intrauterine passage of meconium. METHODS: A pilot study consisting of 10 pregnancies with meconium-stained amniotic fluid and 10 pregnancies with clear amniotic fluid was used. The corresponding plasma and amniotic fluid levels of ZCP were measured using spectrofluorometry. ZCP levels in plasma and amniotic fluid were compared between the two groups and the relation between plasma and amniotic fluid ZCP levels in the clear and meconium-stained groups was assessed using Spearman rank-order correlation. RESULTS: Mean amniotic fluid ZCP was significantly higher in the meconium-stained amniotic fluid as compared to the clear amniotic fluid group. Although mean plasma ZCP levels were higher in the meconium-stained amniotic fluid group, this difference was not statistically significant. There was no significant correlation between plasma ZCP levels and amniotic fluid ZCP, but we could categorize patients according to plasma ZCP levels into four categories with different risks for having meconium-stained amniotic fluid. CONCLUSIONS: Plasma ZCP might be a promising test for prediction of intrauterine passage of meconium in high-risk patients if confirmed by larger studies. The implications of this prediction on management remain unknown.

Adult↗

Amnioinfusion in thick meconium.

OBJECTIVE: There are conflicting reports regarding the results of amnioinfusion in the management of meconium passage in utero. This study was done to evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labour. METHODS: 196 women at term in early labour with meconium were randomized to receive either transcervical intrapartum amnioinfusion with saline (96) or routine obstetrical care (100). Transcervical amnioinfusion of one liter saline infused over 30-45 minutes. End points were relief of decelerations, incidence of vaginal delivery, presence of meconium below the neonatal cords, and X-ray evidence of meconium aspiration. RESULTS: Amnioinfusion resulted in relief of decelerations in 75% of cases as compared to 7% in the control group. Eighty-eight percent of patients delivered vaginally as compared to 58% in the control group (p< 0.001). Neonatal outcome was significantly better in the infusion group. The incidence of meconium below the vocal cords was reduced from 48% to 17% (p< 0.004) using amnioinfusion with positive X-rays for meconium aspiration in only 12.5% versus 26% (p < 0.5). CONCLUSIONS: We concluded that transcervical intrapartum amnioinfusion is a safe, simple and inexpensive technique that reduces operative intervention and improves neonatal outcome, and is of tremendous relevance in developing countries.

Amniotic Fluid↗

Efficacy of bulb versus DeLee suction at deliveries complicated by meconium stained amniotic fluid.

A combined obstetric-pediatric approach to the management of deliveries complicated by meconium-stained amniotic fluid has been recommended to decrease the incidence of meconium aspiration syndrome. Although pharyngeal suction with a DeLee catheter is generally recommended, many obstetricians prefer to use a bulb syringe for suction at the perineum. A thorough review of the literature reveals no prospective studies in humans comparing the two techniques. In the present study, these two techniques of pharyngeal suction were prospectively compared at deliveries complicated by meconium-stained amniotic fluid. Of the total 2874 deliveries, 127 (4%) were complicated by moderate or thickly meconium-stained amniotic fluid, and 107 of these were included in the study. There were 53 infants in the DeLee-suctioned group and 54 in the bulb-suctioned group. Of the 107 studied infants, four (4%) developed meconium aspiration syndrome, three in the DeLee group and one in the bulb group. There was no significant difference in the amount of meconium found below the vocal cords, comparing pharyngeal DeLee suction to bulb suction (0.22 cc versus 0.24 cc; p = NS). In conclusion, the data fail to support a significant difference in efficacy between bulb and DeLee suction in clearing the naso- and oropharynx of the neonate of meconium in cephalic-presenting vaginal or cesarean delivery.

Adult↗

Randomised trial of amnioinfusion during labour with meconium stained amniotic fluid.

OBJECTIVE: To assess the effect of amnioinfusion during labour with meconium stained amniotic fluid on caesarean section rate and perinatal outcome. DESIGN: Prospective randomised controlled study. SETTING: A tertiary care teaching hospital in India. POPULATION: Women in labour at term with meconium stained amniotic fluid. METHODS: Two hundred women in labour with > or = 37 weeks gestation, single cephalic presentation with moderate or thick meconium were randomised to control and amnioinfusion groups at a 1:1 ratio. Amnioinfusion was performed using 500 mL of normal saline over a period of 30 minutes in a study group. The control group received routine care. Both groups had intermittent auscultation of fetal heart rate during labour. MAIN OUTCOME MEASURES: The primary outcome measure was caesarean section rate. Secondary outcome measures were meconium aspiration syndrome, 1 minute and 5 minute apgar < 7, hypoxic ischaemic encephalopathy, neonatal intensive care unit admission, meconium at the level of vocal cords. RESULTS: The caesarean section rate in the amnioinfusion group was less than the control group (RR 0.47; 95% CI 0.24-0.93). Amnioinfusion was associated with a significant decrease in the incidence of meconium at the vocal cords (P = 0.001); improvement in 1 minute apgar scores (P < 0.05), respiratory distress (P = 0.002) and fewer admissions to nursery compared with the controls. This sample size was inadequate to study the impact on meconium aspiration syndrome. CONCLUSION: Amnioinfusion in an under resourced labour ward decreases caesarean section rates and fetal morbidity.

Adult↗

Meconium induces only localized inflammatory lung injury in piglets.

Neonatal meconium aspiration often produces severe respiratory distress due to an inflammatory pulmonary injury, but the extension of this damaging reaction to the noncontaminated lung regions is still uncertain. To investigate the presence of generalized pulmonary inflammatory response, 31 anesthetized and ventilated neonatal piglets (1-3 d) were studied. Meconium (n = 16) or saline (n = 15) was instilled unilaterally into the right lung, and analysis of the lung tissue or bronchoalveolar lavage (BAL) fluid from both lungs was performed after 12 h. Meconium increased the wet/dry weight ratio, histologic tissue injury score and tissue myeloperoxidase activity as well as BAL fluid total cell count in the contaminated lung. Tumor necrosis factor-alfa concentrations in BAL fluid did not however differ significantly. Furthermore, in the meconium-instilled lungs the tissue and lavage fluid catalytic activity of phospholipase A2 (PLA2) and tissue PLA2 group-I and group-II concentrations were significantly elevated. Although BAL fluid catalytic activity of PLA2 was moderately increased also in the meconium noninstilled lung, significant inflammatory injury in this lung was absent. The results thus indicate that meconium aspiration induces severe local inflammation and lung injury, but significant generalized pulmonary inflammatory damage in the pathogenesis of meconium aspiration syndrome is unlikely.

Animals↗

Complement C5a is a key mediator of meconium-induced neutrophil activation.

Meconium aspiration syndrome is a serious condition of the newborn characterized by pulmonary inflammation with substantial neutrophil infiltration. We recently showed that meconium is a potent activator of complement. The aim of the present study was to investigate a possible role for complement in meconium-induced neutrophil activation. Meconium was incubated in human whole blood anticoagulated with lepirudin, a specific thrombin inhibitor that does not affect complement activation. Complement activation was detected by measuring the terminal complement complex. Neutrophil oxidative burst and changes in CD11b and L-selectin expression were measured by flow cytometry. Complement was inhibited using the MAb 166-32 and 137-26, which block factor D and neutralize C5a, respectively. Meconium markedly activated the neutrophils, as revealed by up-regulation of CD11b, accentuation of L-selectin shedding, and induction of oxidative burst. Complement inhibition using the anti-factor D antibody completely (95-100%) blocked meconium-induced changes in CD11b and L-selectin expression, whereas oxidative burst was reduced by 60-70%. The anti-C5a antibody inhibited the neutrophil activation to the same extent as anti-factor D. The data suggest that complement activation is largely responsible for the neutrophil inflammatory responses induced by meconium in vitro and that C5a is a key mediator of this response.

Antibodies, Monoclonal↗

LATE INTESTINAL OBSTRUCTION IN PATIENTS SURVIVING NEONATAL MECONIUM ILEUS.

Two of 15 children who survived neonatal meconium ileus had "meconium ileus equivalent." They were treated with hydration, pancreatic enzyme therapy and antibiotics. One of these children died from pulmonary disease at the time of the bowel obstruction. The survival rate of infants with meconium ileus is steadily improving because of prompt operative intervention, better preoperative and postoperative care and long-term treatment with enzyme supplements and antibiotics. Late intestinal obstruction due to adhesive bands, volvulus, intussusception or "meconium ileus equivalent" may occur in children previously treated for meconium ileus of infancy. The omission of pancreatic enzyme supplementation and the occurrence of respiratory infections are frequently associated with "meconium ileus equivalent."In this series of patients four of the infants treated surgically for neonatal meconium ileus died in the early postoperative period.

Anti-Bacterial Agents↗

Meconium-stained amniotic fluid and fetal oxygen saturation measured by pulse oximetry during labour.

BACKGROUND AND AIM OF THE WORK: The high false-positive rate of electronic fetal heart rate monitoring is the major obstacle to the correct prediction and diagnosis of intrapartum fetal distress. Fetal pulse oximetry is a safe and accurate indicator of fetal oxygenation. The aim of this study was to evaluate the clinical use of this technique for the diagnosis of fetal hypoxia and for prevention of fetal metabolic acidosis and asphyxia during labour, in the presence of meconium-stained amniotic fluid with or without abnormal fetal heart rate patterns, using a threshold value of 30% oxygen saturation. METHODS: Fetal blood oxygen saturation levels (SpO2) of 58 term fetuses with non-reassuring fetal status were measured during labour by fetal pulse oximetry. In 35 cases the amniotic fluid was stained with meconium at onset of labour. Mean SpO2 levels at the different stages of labour were matched against fetal heart rate patterns, the amniotic fluid status, and neonatal outcome. The 35 cases with meconium-stained amniotic fluid were compared with a control group of 28 pregnant women at term who had meconium-stained amniotic fluid during labour but were not monitored by pulse oximetry. RESULTS: When the fetal heart rate tracings were abnormal, mean SpO2values were significantly lower in the first 30 minutes of application and in the last 30 minutes of labour or before Cesarean section. Meconium-stained amniotic fluid was associated with lower SpO2values only when fetal heart monitoring showed a "non-reassuring" pattern. No cases were observed with severe neonatal acidosis, with Apgar score <7 at 5 minutes, or with other adverse neonatal events. In patients with meconium-stained amniotic fluid, neonatal outcomes were better in the group monitored by pulse oximetry versus the control group, although the differences were not statistically significant. CONCLUSIONS: Continued monitoring of fetal oxygen saturation combined with fetal heart rate monitoring may improve accuracy in the evaluation of fetal well-being. As a result, labour could be more safely managed in pregnancies with non-reassuring fetal status as measured by conventional methods, especially in the presence of meconium-stained amniotic fluid.

Adult↗

Direct in vitro effects of meconium on airway reactivity in adult rabbits.

INTRODUCTION: Meconium aspiration syndrome (MAS) is a serious neonatal disease with multifactor pathogenesis and long-term sequelae on the developing respiratory system. Since the altered airway reactivity may play a role in MAS, this study investigated whether 1 hour-lasting in vitro incubation of rabbit tracheal and lung tissue strips with meconium would also increase the airway reactivity. METHODS: Trachea and lungs of adult healthy rabbits were excised. Smooth muscle reactivity was estimated by an in vitro method using organ chambers. After the adaptation of tissue strips, 1 ml of suspended meconium (Meconium) was added into two chambers with one tracheal and one lung strip for another 1 hour. The two other chambers were incubated only with Krebs-Henseleit's buffer (Control). Cumulative doses of histamine (10(-8)-10(-3) mol/l) were added after finishing the incubation period and a continuous recording of contractions was made. RESULTS: The contractile response of the lung tissue smooth muscle to histamine was recorded to decrease non-significantly in Meconium group when compared to Control group. The tracheal tissue reactivity to histamine at concentrations of 10(-8)- 10(-4) mol/l was lower in Meconium group than in Control group. Significant differences appeared only at concentrations of 10(-8), 10(-7), and 10(-6) mol/l (p=0.041, p=0.033, and p=0.019, respectively). CONCLUSIONS: One-hour-lasting in vitro incubation of tracheal and lung tissue strips with meconium significantly decreased the tracheal reactivity to histamine and slightly, but non-significantly decreased the lung tissue reactivity to histamine (Fig. 1, Ref. 6).

Animals↗