Inhibition of pulmonary surfactant function by meconium

MOSES, D. TRAMONTANO. A. C.; Holm, Bruce A.; Spitale, Patricia; Liu, Mingyao; Enhörning, Göran

doi:10.1016/s0002-9378(11)80003-7

Cited by 255 publications

(139 citation statements)

References 19 publications

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“…Other explanations for the inconsistent results of bolus surfactant in these experimentally induced MAS studies include an ongoing inactivation of surfactant by meconium [24,34], and/ or the uneven lung distribution of surfactant when administered by bolus [19,21]. A lavage approach to surfactant administration was consequently described that would theoretically address these concerns.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to mechanical obstruction of the airways and chemical pneumonitis [34], surfactant dysfunction plays a role in the pathophysiology of MAS [4,8,24,32]. To be sure, meconium has been shown to inactivate surfactant both in vitro [4,24] and in vivo [8,32].…”

Section: Introductionmentioning

confidence: 99%

“…To be sure, meconium has been shown to inactivate surfactant both in vitro [4,24] and in vivo [8,32]. This has been the basis for exogenous surfactant administration in this disorder.…”

Section: Introductionmentioning

confidence: 99%

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Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Meister

Balaraman

Ramirez

et al. 2004

Lung

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Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4mg phospholipid/ ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO 2 were observed in the lavage groups compared to the bolus groups and the controls. PaO 2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 ± 54, E-LAVAGE =280 ± 57; I-BOLUS = 139 ± 31; E-BOLUS = 152 ± 29; C = 119 ± 73 (mean ± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of nonhomogeneous lung injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Meister

Balaraman

Ramirez

et al. 2004

Lung

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“…41 This inhibition of surfactant function can be overcome with sufficiently high concentrations of surfactant, 39 suggesting that meconium may inhibit surfactant function by competing with surfactant molecules for space at the air-liquid interface. Bae and colleagues 70 have recently reported the in vitro effects of meconium on the surface tension-lowering properties and the ultrastructural morphology of pulmonary surfactant.…”

Section: Mas and Surfactantmentioning

confidence: 99%

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

Fuloria

Wiswell

1999

J Perinatol

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The term meconium was originally coined by Aristotle who used the Greek word meconium-arion 1 meaning "opium-like," because he believed meconium induced fetal sleep. It is probable that he recognized the association between the presence of meconium in the amniotic fluid and the occurrence of fetal deaths and neonatal depression.Depending on the population studied, the frequency of meconium-stained amniotic fluid (MSAF) at the time of delivery is variable, ranging between approximately 8% and 19% of all term deliveries. [2][3][4][5][6][7][8] Alexander and colleagues 9 noted a 1.5-fold increased risk for MSAF in black women compared with white women. The authors recommended that maternal ethnicity be viewed as a risk indicator of, and not a causal factor for, MSAF. They also observed an increased likelihood of MSAF with increasing gestational age in both ethnic groups.Regardless of the reason for meconium passage, its presence may be associated with adverse fetal and neonatal outcomes, including death, acute respiratory complications, and long-term pulmonary and neurologic abnormalities. Depending on various factors, including the population studied and the criteria used for making a diagnosis, meconium aspiration syndrome (MAS) will develop in 2% to 33% of infants born through MSAF. 3,4,10,11 As many as 30% or more of infants with MAS require mechanical ventilation. 3,12 Accompanying persistent pulmonary hypertension of the newborn (PPHN) is present in approximately one-third of these infants. 13 The mortality associated with MAS is disturbingly high, ranging from 4% to 19% 3,12,14 ; a large proportion of this mortality is attributable to PPHN.Early-onset neonatal seizures, secondary to hypoxic events, have been reported in infants born through thick MSAF. 15 Berkus et al. 16 observed a sevenfold increased risk of neonatal seizures and a fivefold increased likelihood of hypotonia in infants born through moderate to thick compared with thin meconium-stained or clear amniotic fluid. Some investigators have noted an increased likelihood of cerebral palsy in surviving infants with a low Apgar score who were born through MSAF. 17 In addition, there may be long-term pulmonary sequelae associated with MAS. Yuksel et al. 18 have shown increased functional residual capacity and airway reactivity at 6 months of age in infants with MAS; infants who required more respiratory support in the neonatal period had significantly more symptoms and required bronchodilator therapy more often. MAS has also been implicated in increased airway reactivity and abnormal pulmonary function tests in later childhood. 19,20 PATHOPHYSIOLOGY OF MECONIUM PASSAGEMeconium is a viscous green substance composed primarily of water (72% to 80%). Other components of meconium include gastrointestinal secretions, bile, bile acids, mucus, pancreatic juice, cellular debris, and swallowed amniotic fluid, lanugo, vernix caseosa, and blood. 1,21 The substance may first be noted in the fetal gastrointestinal tract as early as 10 to 16 weeks' gestation. At birt...

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“…Surfactant function is inhibited by meconium in a concentration-dependent way. 71,72 Meconium increases the minimum and maximum surface tensions and lowers the surface-spreading rate of surfactant. [71][72][73] Studies of surfactant concentrations and composition in MAS are scarce.…”

Section: Masmentioning

confidence: 99%

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes

et al. 2009

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Deficiency or dysfunction of the pulmonary surfactant plays a critical role in the pathogenesis of respiratory diseases of the newborn. After a short review of the pulmonary surfactant, including its role in selected neonatal respiratory conditions, we describe a series of studies conducted by applying two recently developed methods to measure surfactant kinetics. In the first set of studies, namely 'endogenous studies', which used stable isotope-labeled intravenous surfactant precursors, we have shown the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors, including plasma glucose, plasma fatty acids and body water. In the second set of studies, namely 'exogenous studies', which used a stable isotope-labeled phosphatidylcholine (PC) tracer given endotracheally, we estimated the surfactant disaturated phosphatidylcholine (DSPC) pool size and half-life. The major findings of our studies are presented here and can be summarized as follows: (a) the de novo synthesis and turnover rates of the surfactant (DSPC) in preterm infants with respiratory distress syndrome (RDS) are very low with either precursor; (b) in preterm infants with RDS, pool size is very small and half-life much longer than what has been reported in animal studies; (c) patients recovering from RDS who required higher continuous positive airway pressure pressure after extubation or reintubation have a lower level of intrapulmonary surfactant than those who did well after extubation; (d) term newborn infants with pneumonia have greatly accelerated surfactant catabolism; and (e) infants with uncomplicated congenital diaphragmatic hernia (CDH) and on conventional mechanical ventilation have normal surfactant synthesis, but those requiring extracorporeal membrane oxygenated (ECMO) do not. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

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Inhibition of pulmonary surfactant function by meconium

Cited by 255 publications

References 19 publications

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes

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