Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. (1/54)

Mouse null mutants of transcription factor ATF-2 were generated by the gene targeting method. They died shortly after birth and displayed symptoms of severe respiratory distress with lungs filled with meconium. These features are similar to those of a severe type of human meconium aspiration syndrome. The increased expression of the hypoxia inducible genes suggests that hypoxia occurs in the mutant embryos and that it may lead to strong gasping respiration with consequent aspiration of the amniotic fluid containing meconium. A reduced number of cytotrophoblast cells in the mutant placenta was found and may be responsible for an insufficient supply of oxygen prior to birth. Using the cDNA subtraction and microarray-based expression monitoring method, the expression level of the platelet-derived growth factor receptor alpha gene, which plays an important role in the proliferation of trophoblasts, was found to be low in the cytotrophoblasts of the mutant placenta. In addition, ATF-2 can trans-activate the PDGF receptor alpha gene promoter in the co-transfection assay. These results indicate the important role of ATF-2 in the formation of the placenta and the relationship between placental anomalies and neonatal respiratory distress. The ATF-2 null mutants should enhance our understanding of the mechanism of severe neonatal respiratory distress.  (+info)

A randomised control study of partial liquid ventilation after airway lavage with exogenous surfactant in a meconium aspiration syndrome animal model. (2/54)

AIMS: To test the hypothesis that lavage with exogenous surfactant before partial liquid ventilation in meconium aspiration syndrome (MAS) would improve debris removal, and therefore the effectiveness of partial liquid ventilation. METHODS: 12 newborn piglets were randomised into 4 groups, partial liquid ventilation or gas ventilation, with and without surfactant lavage. Physiological and blood gas data were compared between groups by analysis of variance. RESULTS: Arterial oxygen pressure (PaO(2)) was improved in the group treated with surfactant lavage when compared with the group not receiving surfactant. PaO(2) in the group receiving surfactant lavage followed by partial liquid ventilation was further improved when compared with the group treated with surfactant lavage followed by gas ventilation and the group receiving partial liquid ventilation alone. CONCLUSION: The effectiveness of partial liquid ventilation in MAS might be enhanced by pretreatment with exogenous surfactant bronchial lavage.  (+info)

Hemodynamic effects of periodic G(z) acceleration in meconium aspiration in pigs. (3/54)

The hemodynamic effects of periodic acceleration (pG(z)), induced in the spinal axis with noninvasive motion ventilation (NIMV), were studied in a piglet model of pulmonary hypertension associated with meconium aspiration. Animals (n = 12) were anesthetized, paralyzed, intubated, and supported by conventional mechanical ventilation (CMV). Thirty minutes after tracheal instillation of meconium solution (6 ml/kg), either CMV (n = 6) was continued or NIMV (n = 6) was initiated. Changes in systemic and pulmonary hemodynamics and arterial blood gases were tracked for 2 h after aspiration. Thermodilution, cardiac output, and heart rate were not significantly different after meconium aspiration in the pG(z) group relative to the CMV controls. Aortic pressure and systemic vascular resistance were significantly lower (approximately 30%) after meconium aspiration in NIMV animals relative to CMV animals. Pulmonary arterial pressure and pulmonary vascular resistance were also significantly lower, by 100%, after aspiration of meconium in the NIMV animals compared with the CMV controls. Meconium aspiration significantly decreased total respiratory compliance by approximately 50% and increased total respiratory resistance by approximately 100% in both CMV and NIMV animals, but such alterations did not differ between the two groups. Both CMV and NIMV satisfactorily supported ventilation in these paralyzed animals. In conclusion, NIMV through pG(z) in the spinal axis decreased systemic and pulmonary vascular resistance in piglets after meconium aspiration.  (+info)

Beat-to-beat changes in stroke volume precede the general circulatory effects of mechanical ventilation: a case report. (4/54)

BACKGROUND: The haemodynamic as well as the ventilatory consequences of mechanical ventilation can be harmful in critically ill neonates. Newly developed ventilatory lung protective strategies are not always available immediately and in an acute situation the haemodynamic changes caused by mechanical ventilation can affect the oxygen delivery considerably. We report the case of a male neonate who was treated with conventional pressure-controlled mechanical ventilation because of respiratory distress and progressive respiratory acidosis resulting from meconium aspiration. Because of poor arterial oxygenation despite 100% inspired oxygen and increased ventilator settings, echocardiography was performed to exclude central haemodynamic reasons for low oxygen delivery. METHOD: Doppler echocardiography was used for the measurement of stroke volume and cardiac output. Pulse oximetry and aortic blood pressure were monitored continuously. RESULTS: Echocardiography revealed no cardiac malformations or signs of persistent fetal circulation. When inspiratory pressures and duration were increased, beat-to-beat variation in stroke volume preceded decay in cardiac output. Stroke volume variations and oxygen saturation values guided ventilator settings until extracorporal membrane oxygenation could be arranged for. After recovery and discharge 4 weeks later the boy is progressing normally. CONCLUSION: Because oxygen delivery is dependent on both blood flow and arterial oxygen content, measurement of cardiac output as well as left heart oxygen saturation is a useful guide to optimizing oxygen delivery. This case report demonstrates how Doppler echocardiographic monitoring of beat-to-beat changes in stroke volume can be used to detect early negative haemodynamic effects of increased mechanical ventilation settings before cardiac output is affected.  (+info)

A comparison of surfactant delivery with conventional mechanical ventilation and partial liquid ventilation in meconium aspiration injury. (5/54)

The objective of this study was to compare surfactant (SF) distribution and physiological effects after standard SF delivery during conventional mechanical ventilation (CMV) with that using partial liquid ventilation (PLV). A model of meconium aspiration syndrome (MAS) was developed using two groups of adult rats (n = 14). After meconium instillation of 2.5 ml kg(-1) (20% v/w), SF/CMV: (n = 7) CMV and SF/PLV: (n = 7) PLV, received 14C-labeled surfactant (4 ml kg(-1)) delivered intratracheally in four aliquots over 20 min in both groups. Sequential measurements of arterial blood chemistry and lung mechanics were performed in all animals. At the conclusion of experiments, lungs were inflated (30 cmH2O), dried, sectioned and evaluated for radioactivity in disintegrations per minute (DPM). Surfactant distribution was improved (P< 0.01) with PLV as compared to CMV with 48.8% of the pieces vs. 30.9% of the pieces receiving within 25% of the mean amount of surfactant, respectively. Further, regional distribution was also significantly more uniform with PLV than CMV: left vs right (P<0.01) lung and ventral vs. dorsal (P<0.01) regions. Finally, arterial PO2 and ventilation efficiency index were significantly (P<0.01) greater post-treatment in SF/PLV than SF/CMV. These data demonstrate surfactant delivery with PLV, as compared to CMV alone, to be an improved method of delivering surfactant in MAS and suggest the possible utility of SF/PLV combination therapy for its treatment of other etiologies of neonatal respiratory distress.  (+info)

The effects of amnioinfused solutions for meconium-stained amniotic fluid on neonatal plasma electrolyte concentrations and pH. (6/54)

OBJECTIVE: To determine if amnioinfused normal saline or lactated Ringer's solution in cases of meconium-stained amniotic fluid is associated with significant changes on neonatal plasma electrolyte concentrations or pH. STUDY DESIGN: This was a prospective randomized study using normal saline or lactated Ringer's solution for amnioinfusion in women with thick meconium in the amniotic fluid. The control group was composed of women with clear amniotic fluid not receiving amnioinfusion. Cord blood arterial sampling was analyzed for sodium, potassium, and chloride plasma concentrations and pH. The sample sizes allowed for an alpha of 0.05 and power of 0.80. RESULTS: We evaluated 61 cases (20 normal saline solution, 20 lactated Ringer's solution, and 21 control). No significant differences in cord blood arterial plasma concentrations of sodium (p=0.43), potassium (p=0.21), chloride (p=0.68), and pH (p=0.11) were noted. CONCLUSION: Use of normal saline or lactated Ringer's solution for amnioinfusion in meconium-stained amniotic fluid is not associated with changes on neonatal plasma electrolyte concentrations or pH.  (+info)

Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model. (7/54)

Meconium aspiration syndrome is a cause of significant morbidity and mortality in the perinatal period and has been implicated in the pathogenesis of airway dysfunction. In this study, we developed a murine model to evaluate the effects of meconium aspiration on airway physiology and lung cellular responses. Under light anesthesia, BALB/c mice received a single intratracheal instillation of meconium or physiological saline. Respiratory mechanics were measured in unrestrained animals and expressed as percent increase in enhanced pause to increasing concentrations of methacholine (MCh). Furthermore, we assessed the changes in cells and cytokines into the bronchoalveolar lavage fluid (BALF). We found meconium aspiration produced increased airway responsiveness to MCh at 7 days. These functional changes were associated with lymphocytic/eosinophilic inflammation, goblet cell metaplasia, and increased concentrations of IL-5 and IL-13 in the BALF. Our findings suggest meconium aspiration leads to alterations of airway function, lung eosinophilia, goblet cell metaplasia, and cytokine imbalance, thus providing the first evidence of meconium-induced airway dysfunction in a mouse model.  (+info)

Endothelin 1 concentrations in infants with meconium stained amniotic fluid. (8/54)

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.  (+info)

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