Comparison of Pulmonary and Inflammatory Effects of Lipid- and Water-Soluble Components in Meconium in Newborn Piglets

Abstract

To understand the pathogenesis of meconium aspiration syndrome, we compared the pulmonary and inflammatory effects of the water and lipid extracts of human meconium instilled into the lungs of newborn piglets. The piglets were artificially ventilated, made hypoxemic, and randomized into three groups. At start of reoxygenation, 3 ml/kg of one of the following mixtures was instilled intratracheally: (1) meconium (n = 12); (2) water extract of meconium (n = 12), and (3) lipid extract of meconium (n = 12). During 8 h of reoxygenation, hemodynamics, pulmonary gas exchange, lung mechanics, and interleukin-8 concentrations in tracheobronchial aspirates were monitored. Oxygenation index (p = 0.04) and mean airway pressure (p = 0.04) increased more in the lipid extract group than in the water extract group. Dynamic compliance and mean arterial blood pressure decreased (p < 0.05) in the meconium and lipid extract groups, but not in the water extract group. At 8 h of reoxygenation, the interleukin-8 concentration in the tracheobronchial aspirates was three times higher in the lipid extract group as compared with the water extract group (110 ± 102 vs. 37 ± 27 pg/ml; p = 0.02). In conclusion, pulmonary dysfunction in meconium aspiration syndrome is caused by both the water- and lipid-soluble fractions of meconium, with stronger inflammatory and more detrimental effects promoted by the lipid extract than the water extract.

Meconium-induced inflammation and surfactant inactivation: specifics of molecular mechanisms

“…Both fractions of meconium impair surfactant, but the lipidsoluble fraction containing cholesterol, FFAs (mainly palmitic, stearic, and oleic acids), and triglycerides had stronger effect than the aqueous fraction (12), and lipid-soluble extract of meconium closely stimulated DPPC inhibition due to whole meconium (13).…”

“…Such direct inactivation regards both the endogenous and exogenous surfactant (10,11). Being composed of amniotic fluid, desquamated epithelial cells, lanugo, vernix caseosa, mucus, blood, and gastrointestinal secretions swallowed during the intrauterine life, both hydrophobic and hydrophilic material can be found in meconium mess: cholesterol, free fatty acids (FFAs), and triglycerides in chloroform-soluble fraction and bile acids, bilirubin, dietary fiber, hemoglobin, proteins, and inorganic molecules in water-or water-methanol-soluble fraction (9,(11)(12)(13). When present, meconium alters structure of the major surfactant phospholipid (PL) dipalmitoylphosphatidylcholine (DPPC), causes fragmentation of its bilayer, and disrupts function of liposomes.…”

Toxic effects of different meconium fractions on lung function: new therapeutic strategies for meconium aspiration syndrome?

“…12,13 In the second study 3 ml kg À1 body weight of either meconium, lipid-or water-soluble meconium fractions was instilled intratracheally in separate groups. 14 In the third study a moderate and severe model was developed. A moderate MAS was developed by instilling meconium of 4 ml kg À1 body weight, giving an OI of approximately 12.…”

“…Intact meconium had more severe effects on the lungs than the lipid-and water-soluble fractions of meconium separately. 14 …”

Efeitos da adição de polietilenoglicol ao surfactante exógeno no tratamento da síndrome de aspiração de mecônio em coelhos recém-nascidos

“…(Günther, 2001). Como os pequenos agregados desempenham pior atividade tensoativa, a alta relação PA/GA está relacionada com piora da função do surfactante (Ochs et al, 2006 (Robertson e Lachmann, 1988;Sun et al, 1993a;Tashiro et al, 2003;Tollofsrud et al, 2003) e mostra que a presença de mecônio nas vias aéreas distais pode causar anormalidades na função do surfactante devido à inibição ou alteração na composição, resultando em diminuição da complacência pulmonar, diminuição da capacidade residual funcional, atelectasia e hipoxia (Brown e Pattishal, 1993;Cleary et al, 1997;Kattwinkel, 1998 Introdução contribuem para a inativação do surfactante (Holm et al, 1988;Davey et al, 1993;Sun et al, 1993a). …”