Glycyrrhizic acid alleviates the meconium-induced acute lung injury in neonatal rats by inhibiting oxidative stress through mediating the Keap1/Nrf2/HO-1 signal pathway.

Meconium aspiration syndrome (MAS) is a disease closely related to inflammation and oxidative stress. Glycyrrhizic acid (GA) is a triterpenoid isolated from licorice with multiple bioprotective properties. In the present study, impacts of GA against MAS rats, as well as the potential mechanism, will be investigated. MAS model was established on newborn rats, followed by the treatment of 12.5, 25, and 50 mg/kg GA. The wet/dry weight ratio of lung tissues was calculated. The production of IL-6, IL-1ß, TNF-α, malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) was measured using ELISA assay. HE staining was used to evaluate the pathological state of lung tissues and TUNEL assay was used to detect the apoptotic state. The protein expression of Nrf2, Keap1, HO-1, Bcl-2, Bax, and cleaved-Caspase3 was measured by Western blotting assay. The elevated W/D ratio, release of inflammatory factors, lung injury score, and apoptotic index, as well as the activated oxidative stress and suppressed Keap1/Nrf2/HO-1 pathway, in MAS rats were significantly alleviated by GA. After introducing the inhibitor of Nrf2, ML385, the protective property of GA on the pathological state, apoptotic index, and oxidative stress in MAS rats was pronouncedly abolished. Taken together, glycyrrhizin alleviated GAH in rats by suppressing Keap1/Nrf2/HO-1 signaling mediated oxidative stress.

Pathophysiological effects of intravenous phosphodiesterase type 4 inhibitor in addition to surfactant lavage in meconium-injured newborn piglet lungs.

BACKGROUND: Nonsteroidal anti-inflammatory drugs, such as selective phosphodiesterase type 4 (PDE4) inhibitors have potential anti-inflammatory and respiratory smooth muscle relaxation effects. This study aimed to investigate the pathophysiological effects of an intravenous PDE4 inhibitor (rolipram) and surfactant lavage (SL) in a newborn piglet model of meconium aspiration syndrome (MAS). METHODS: MAS was induced in 25 newborn piglets, which were randomly divided into control and four SL treatment groups administered with different doses of intravenous rolipram (0, 0.1, 0.5, and 1 mg/kg). Cardiopulmonary variables were monitored and recorded. The experimental time was 4 hours. Serial blood was drawn for blood gas and biomarker analyses. Lung tissue was examined for histological analysis. RESULTS: All SL-treated groups revealed improved oxygenation during the 4-hour experiments and had significantly lower peak inspiratory pressure levels than the control group at the end of experiments. All SL plus rolipram-treated groups exhibited significantly higher lung compliance than the control group. However, the animals receiving high-dose (0.5 and 1.0 mg/kg) rolipram demonstrated significantly elevated heart rates. Lung histology of the nondependent sites revealed significantly lower lung injury scores in all SL-treated groups compared with that in the control group, but there were no differences among the rolipram-treated groups. CONCLUSIONS: In addition to SL, intravenous PDE4 inhibitors may further improve lung compliance in treating MAS; however, it is necessary to consider cardiovascular adverse effects, primarily tachycardia. Further investigations are required before the clinical application of intravenous PDE4 inhibitor as an anti-inflammatory agent to treat severe MAS.

Early cardiac injury in acute respiratory distress syndrome: comparison of two experimental models.

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.

Meconium aspiration pneumonia and otitis media in two goat kids.

We report meconium aspiration in 2 sibling goat kids, and characterize the expected lesions of aspiration pneumonia in conjunction with the rare lesion of otitis media. Grossly, the lungs were multifocally consolidated, and there was yellow-green exudate within the middle ear. Histologically, the lung was characterized by pyogranulomatous pneumonia and foreign-body reaction around aspirated debris. Within the lumen of the middle ear, aspirated squamous cells, keratin, meconium debris, and neutrophils, without evidence of bacteria, were accompanied by a subepithelial accumulation of lymphocytes, plasma cells, and fewer macrophages. This is an especially rare phenomenon, which is thought to result from transport of meconium from the oropharynx through the auditory tube (Eustachian tube) to the middle ear.

Degradation of Lung Protective Angiotensin Converting Enzyme-2 by Meconium in Human Alveolar Epithelial Cells: A Potential Pathogenic Mechanism in Meconium Aspiration Syndrome.

BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2. METHODS: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium, meconium + a protease inhibitor cocktail (PIc) and PIc alone for 16 h. At the end of incubation, apoptosis was measured with a nuclear fragmentation assay and cell lysates were collected for ACE-2 immunoblotting and enzyme activity. RESULTS: Meconium caused a fourfold increase in apoptotic nuclei (p < 0.001). The pro-apoptotic effect of meconium can be reversed by PIc. Meconium reduced ACE-2 enzyme activity by cleaving ACE-2 into a fragment detected at ~ 37 kDa by immunoblot. PIc prevented the degradation of ACE-2 and restored 50% of ACE-2 activity (p < 0.05). CONCLUSION: These data suggest that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium, since the effects of meconium can be reversed by PIc.

Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome.

PURPOSE: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. METHODS: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. RESULTS: The BAL fluid TNF-α, IL-1ß, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION: Meconium-induced inflammatory cytokine production is affected by the body temperature control.

Effects of hypothermia on lung inflammation in a rat model of meconium aspiration syndrome

Abstract Purpose: To evaluate the effects of hypothermia treatment on meconium-induced inflammation. Methods: Fifteen rats were instilled with human meconium (MEC, 1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. Eight rats that were ventilated and not instilled with meconium served as a sham group. In MEC-hypothermia group, the body temperature was lowered to 33±0.5°C. Analysis of the blood gases, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage (BAL) fluid samples, and histological analyses of the lungs were performed. Results: The BAL fluid TNF-α, IL-1β, IL-6 and IL-8 concentrations were significantly higher in the MEC-hypothermia group than in the MEC-normothermia (p < 0.001, p < 0.001, p = 0.001, p < 0.001, respectively) and sham-controlled groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). Conclusion: Meconium-induced inflammatory cytokine production is affected by the body temperature control.

Modified porcine surfactant enriched by recombinant human superoxide dismutase for experimental meconium aspiration syndrome.

AIMS: Combination of exogenous surfactant with antioxidant enzyme recombinant human superoxide dismutase (rhSOD) was tested in the treatment of experimental meconium aspiration syndrome as oxidative processes play key role in its pathogenesis. MATERIAL AND METHODS: Young New Zealand rabbits were instilled by saline (Sal group) or by meconium suspension (Mec group). Some of meconium-instilled animals were treated by surfactant alone (Surf group) or surfactant in combination with rhSOD (Surf + SOD group) and oxygen-ventilated for 5 h. PaO2/FiO2, oxygenation index, oxygen saturation, PaCO2, ventilation efficiency index and alveolar-arterial gradient were evaluated every hour; post mortem, cells in bronchoalveolar lavage were counted, inflammatory and oxidative markers were assessed using ELISA in lung tissue homogenates. KEY FINDINGS: Exogenous surfactant combined with rhSOD improved oxygenation during the first hour after the treatment more than surfactant alone (p = 0.039 to 0.0001 vs. Mec and Surf group). Amelioration was also seen in CO2 elimination (p = 0.049 to 0.0096 vs. Mec group), alveolar-arterial gradient diminution (p = 0.024 to 0.0019 vs. Mec and Surf group), prevention of oxidative damage and cytokine production (p = 0.049 to 0.002 vs. Mec group). SIGNIFICANCE: It seems that inhibition of oxidative signalization may be strong supporting factor in surfactant treatment of MAS.

Comparison of different dosing strategies of intratracheally instilled budesonide on meconium injured piglet lungs.

BACKGROUND: Severe inflammation plays a vital role in the pathogenesis of meconium aspiration syndrome (MAS). Intratracheal (IT) instillation of corticosteroids may be beneficial for MAS in optimizing local effect and reducing systemic adverse effects, but the optimum dosing course remains open to question. METHODS: Thirty meconium-injured newborn piglets were enrolled into six study groups. The first four groups consisted of the IT instillation of 0.25/0.5 mg/kg using either one (IT-B251/IT-B501) or two (IT-B252/IT-B502) doses of budesonide, while the other two groups were the intravenous (IV) dexamethasone (0.5 mg/kg) (IV-Dex) group and the control group (Ctrl). Vital signs and cardiopulmonary functions were monitored throughout the experiments. Pulmonary histology was examined after completing the experiments. RESULTS: Both the IV-Dex and IT-B501 groups got significant improvement in oxygenation (P < 0.05). Lung compliance became worse after one dose of 0.25 mg/kg of IT budesonide. Pulmonary histology revealed that there were significantly lower lung injury scores for all treatment groups compared to control group, especially at the non-dependent sites of both the IT-B501 and IT-B502 groups. There was no significant difference between double- and single-dose groups, no matter whether 0.25 or 0.5 mg/kg of budesonide was used. CONCLUSIONS: IT instillation of one dose of 0.5 mg/kg budesonide is beneficial in treating meconium-injured piglet lungs during the first 8 h of injury, but a second dose at an interval of 4 h does not have a superior beneficial effect compared to one dose.

Lung ultrasonography to diagnose meconium aspiration syndrome of the newborn.

Objective To investigate the diagnostic value of lung ultrasonography for neonatal meconium aspiration syndrome (MAS). Methods This prospective observational study enrolled patients diagnosed with MAS based on medical history, clinical manifestations and chest X-ray and control newborns without MAS. During ultrasonography, each lung was divided into three regions (front, lateral, and back), using anterior and posterior axillary lines as the boundary. While scanning each region of the lungs, the hand piece was perpendicular or parallel to the ribs. Results This study enrolled 117 newborns with MAS and 100 controls. The main lung ultrasonographic findings in patients with MAS were: (i) pulmonary consolidation with air bronchogram was found in all patients; (ii) pleural line anomalies and the disappearance of the A-line was found in all patients; (iii) atelectasis was found in 19 (16.2%) severe cases, who demonstrated severe massive atelectasis and visible lung pulse; (iv) pleural effusion was found in 16 patients (13.7%); and (v) alveolar-interstitial syndrome or B-line in the non-consolidation area was found in all patients with MAS. Conclusion Ultrasonography can be used routinely to diagnose MAS in an accurate, reliable, convenient, and non-invasive manner.

Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome.

BACKGROUND: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). PURPOSE OF THE STUDY: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. MATERIALS AND METHODS: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham-controlled group. Analysis of the blood gases, interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. RESULTS: Intrapulmonary instillation of meconium resulted in the increase of TNF-α (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1ß, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). CONCLUSION: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements.

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs.

OBJECTIVES: To evaluate the combined effects of surfactant lavage and intratracheally instillation of budesonide on meconium-injured piglet lungs. DESIGN: A prospective, randomized, animal model study. SETTING: An experimental laboratory. SUBJECTS: Twenty-four anesthetized and mechanically ventilated newborn piglets. INTERVENTIONS: Human meconium slurry was intratracheally instilled into piglet lungs to induce lung injury. The injured piglets were randomly assigned to either the sham treatment group (control) or one of the three therapeutic groups: the intratracheally instilled budesonide (Bud) group, the bronchoalveolar lavage with diluted surfactant (dsBAL) group, and the combination therapy of Bud and dsBAL (dsBAL + Bud) group. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary profiles were measured hourly. Proinflammatory cytokine (interleukin-1ß, interleukin-6, and interleukin-8) levels in bronchoalveolar lavage fluid were measured. Finally, the pulmonary histology of the experimental subjects was examined at the end of experiments. Both of the lavaged groups (dsBAL and dsBAL + Bud) showed significantly better oxygenation than those that had not undergone lavage (control and Bud) (p < 0.05). The dsBAL + Bud group showed a significantly higher lung compliance and required a significantly lower peak inspiratory pressure during the experimental periods than the other three groups (p < 0.05). All treatment groups had significantly lower concentrations of interleukin-1ß concentration in the bronchoalveolar lavage fluid than the control group (p < 0.05). The dsBAL + Bud group also had a significantly lower interleukin-6 concentration in the bronchoalveolar lavage fluid (p< 0.05), as well as a significantly lower lung injury score based on pulmonary histology than the control group (p < 0.05). CONCLUSIONS: Therapeutic bronchoalveolar lavage with diluted surfactant followed by intratracheal instillation of budesonide has a synergistic and beneficial effect when treating severe meconium-injured newborn piglet lungs.

A case report of an asymptomatic late term abdominal pregnancy with a live birth at 41 weeks of gestation.

BACKGROUND: Despite advances in diagnostic imaging and focused antenatal care, cases of undiagnosed abdominal pregnancies at term are still reported in obstetric practice. It is atypical and very rare for a patient to be asymptomatic late in pregnancy and for the pregnancy to result in a live birth with no evidence of intrauterine growth restriction despite the unfavourable implantation site. This late term asymptomatic presentation despite routine antenatal care demonstrates a diagnostic challenge. CASE PRESENTATION: We report a case of a 26 year old Primigravida with an asymptomatic and undiagnosed abdominal pregnancy carried beyond 41 weeks of gestation espite routine antenatal care and serial ultrasound reports. She presented for a routine antenatal care visit at 41 weeks of gestation. Induction of labour was initiated due to the late term gestation but was unsuccessful. At this point the fetus developed severe tachycardia and CTG confirmed persistent non-reassuring foetal heart rate patterns. The mother was then prepared for an emergency caesarean delivery. Abdominal pregnancy was only diagnosed at laparotomy where a term male baby weighing 3108 g was delivered with an Apgar Score of 7 and 8 at 1 and 5 min respectively. The placenta which was implanted into the omentum, ileal mesentery and extending to the pouch of Douglas was removed following active bleeding from its detached margins. She was transfused with two units of blood and four units of fresh frozen plasma. Postoperative morbidity was minimal with transient paralytic ileus on the second post-operative day. Her recovery was otherwise uneventful and she was discharged on the seventh post-operative day in good condition. The neonate developed meconium aspiration syndrome and passed away on the 2nd day of life despite having undergone standard care. A post-mortem examination was not performed because the family did not consent to the procedure. Follow up of the mother at 2, 6 weeks and 6 months postpartum was uneventful. CONCLUSIONS: This atypical presentation of an asymptomatic abdominal pregnancy carried tolate term and only diagnosed at laparotomy despite routine antenatal care demonstrates a significant lapse in diagnosis. Clinicians and radiologists must always bear this possibility in mind during routine client evaluation. Skills training in Obstetric ultrasound and in the clinical assessment of obstetric patients should emphasize features suggestive of abdominal pregnancy. This will improve diagnosis, ensure appropriate management and minimise complications. Immediate termination of pregnancy can be offered if the diagnosis is made before 20 weeks of gestation. Patients diagnosed with advanced abdominal pregnancies and are stable can be monitored under close surveillance and delivered at 34 weeks of gestation after lung maturity is achieved. Although removal of the placenta carries a higher risk of haemorrhage, a partially detached placenta can be delivered with minimal morbidity and a good maternal outcome. Given the documented low survival rates of neonates in such cases, neonatal units must be adequately equipped and staffed to support them. Post-mortem examination is important to confirm cause of death and exclude other complications and congenital anomalies. Communities need to be educated about the importance of this procedure.

Histologic Evidence of Intrapulmonary Bronchopulmonary Anastomotic Pathways in Neonates with Meconium Aspiration Syndrome.

We examined lung histology from 8 infants who died with meconium aspiration syndrome in order to determine the presence of intrapulmonary bronchopulmonary anastomotic pathways. Each infant required mechanical ventilation to treat hypoxemic respiratory distress. Lung histology from each infant shows evidence of prominent bronchopulmonary vascular connections.

Consequences of meconium stained amniotic fluid: what does the evidence tell us?

BACKGROUND: Meconium stained amniotic fluid (MSAF) is common and associated with meconium aspiration syndrome (MAS). Other consequences of meconium passage before birth are less well understood. METHODS: We reviewed the literature for original papers reporting on outcomes associated with MSAF. FINDINGS: Among preterm infants MSAF is more prevalent than previously believed and is associated with higher neonatal morbidity. Intrauterine exposure to meconium is associated with inflammation of tissues of the lung, chorionic plate and umbilical vessels and through various mechanisms may contribute to neonatal morbidity, independent of MAS. No compelling evidence supported an association between MSAF and increased neurological impairment, including early seizure activity.

Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome.

BACKGROUND: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. OBJECTIVE: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. METHODS: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. RESULTS: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. CONCLUSION: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome.

A case of meconium aspiration syndrome in a bottlenose dolphin (Tursiops truncatus) calf.

Stillbirth and neonatal mortality are significant problems in captive breeding of dolphins, however, the causes of these problems are not fully understood. Here, we report a case of meconium aspiration syndrome (MAS) in a male neonate of bottlenose dolphin (Tursiops truncates) who died immediately after birth. At necropsy, a true knot was found in the umbilical cord. The lungs showed diffuse intraalveolar edema, hyperemic congestion and atelectasis due to meconium aspiration with mild inflammatory cell infiltration. Although the exact cause of MAS in this case was unknown, fetal hypoxia due possibly to the umbilical knot might have been associated with MAS, which is the first report in dolphins. MAS due to perinatal asphyxia should be taken into account as a possible cause of neonatal mortality and stillbirth of dolphin calves.

Diagnosis-related deterioration of lung function after extracorporeal membrane oxygenation.

The aim of the study was to assess lung function longitudinally after neonatal extracorporeal membrane oxygenation (ECMO), and to identify any effects of diagnosis and perinatal characteristics. 121 neonatal ECMO-treated children (70 with meconium aspiration syndrome, 20 congenital diaphragmatic hernia and 31 with other diagnoses) performed a total of 191 lung function measurements at 5, 8 and/or 12 yrs. We assessed dynamic and static lung volumes, reversibility of airway obstruction and diffusion capacity. Mean SDS forced expiratory volume in 1 s (FEV(1)) at 5 yrs before and after bronchodilation (-0.51 and 0.07) was significantly higher than at 8 (-0.79 and -0.4; p<0.04) and 12 yrs (-1.10 and -0.52; p<0.003). Mean SDS for all spirometric parameters before and after bronchodilation were significantly lower in the congenital diaphragmatic hernia group compared with the other diagnostic groups (all p ≤ 0.025). A significant volume of trapped air was observed in 86% patients with congenital diaphragmatic hernia, 50% with meconium aspiration syndrome and 58% with other diagnoses. After bronchodilation, mean SDS FEV(1) and forced vital capacity were negatively influenced by duration of ventilation (both p<0.001) and duration of ECMO (p=0.003 and p=0.02, respectively). Long-term pulmonary sequelae after neonatal ECMO-treatment mainly occur in congenital diaphragmatic hernia patients and tend to deteriorate over time.

The effects of pentoxifylline on lung inflammation in a rat model of meconium aspiration syndrome.

To examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord.

OBJECTIVE: To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. STUDY DESIGN: We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. RESULTS: Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. CONCLUSIONS: Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.