Role of Meconium and Hypoxia in Meconium Aspiration-Induced Lung Injury in Neonatal Rabbits

Zagariya, Alexander; Sierzputovska, Monica; Navale, Shan; Vidyasagar, Dharmapuri

doi:10.1155/2010/204831

Cited by 11 publications

(18 citation statements)

References 17 publications

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“…High-frequency oscillatory ventilation may be beneficial in clinical MAS complicated by pulmonary interstitial emphysema [20]. Zagariya et al [21] used an animal model and compared the effects of saline, milk and meconium instillation into the rabbit lungs. They further used an in vitro cell model with hypoxia-, hyperoxia- and meconium-treated cells.…”

Section: Inflammation In Mas - Lessons Learned From Experimental Studiesmentioning

confidence: 99%

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

et al. 2015

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Does meconium cause meconium aspiration syndrome (MAS) or is meconium discharge only a marker of fetal hypoxia? This dispute has lasted for centuries, but since the 1960s, detrimental effects of meconium itself on the lungs have been demonstrated in animal experiments. In clinical MAS, persistent pulmonary hypertension of the newborn is the leading cause of death in MAS. Regarding the complex chemical composition of meconium, it is difficult to identify a single agent responsible for the pathophysiology. However, considering that meconium is stored in the intestines, partly unexposed to the immune system, aspirated meconium could be recognized as ‘danger', representing damaged self. The common denominator in the pathophysiology could therefore be activation of innate immunity. Thus, a bulk of evidence implies that meconium is a potent activator of inflammatory mediators, including cytokines, complement, prostaglandins and reactive oxygen species. We hypothesize that the two main recognition systems of innate immunity, the Toll-like receptors and the complement system, recognize meconium as ‘danger', which leads not only to lung dysfunction but also to a systemic inflammatory response. This might have therapeutic implications in the future.

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Section: Inflammation In Mas - Lessons Learned From Experimental Studiesmentioning

confidence: 99%

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

et al. 2015

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“…Experimental studies have revealed that meconium induces a potent local inflammation in the lungs, with the features: leukocyte infiltration, alveolar macrophage activation, the release of myeloperoxidase (MPO), increased cytokine formation, and apoptosis [5]. Additionally, MAS-induced complement activation and cytokine release has been shown experimentally in piglets [6], and the systemic inflammatory response has been shown to correlate with the severity of MAS among neonates [7].…”

Section: Introductionmentioning

confidence: 99%

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

et al. 2018

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Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.

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“…4, 65–69 The pathophysiology has been attributed to: 1) the mechanical effect of meconium, which can obstruct the airways, and 2) the inflammatory effect of meconium. 68, 70 We propose that intra-amniotic inflammation due to intra-amniotic infection or sterile intra-amniotic inflammation accompanied by a fetal inflammatory response predisposes fetuses exposed to MSAF to develop MAS.…”

Section: Introductionmentioning

confidence: 99%

Meconium aspiration syndrome: a role for fetal systemic inflammation

Lee

Romero

Lee

et al. 2016

American Journal of Obstetrics and Gynecology

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Background Meconium aspiration syndrome (MAS) is a leading cause of morbidity and mortality in term infants. Meconium-stained amniotic fluid (MSAF) occurs in approximately one of every seven pregnancies, but only 5% of neonates exposed to MSAF develop MAS. Why some infants exposed to meconium develop MAS while others do not is a fundamental question. Patients with MSAF have a higher frequency of intra-amniotic infection/inflammation than those with clear fluid. We propose that fetal systemic inflammation is a risk factor for the development of MAS in patients with MSAF. Objective To investigate whether intra-amniotic inflammation and funisitis, the histopathologic landmark of a fetal inflammatory response, predispose to MAS. Study Design A prospective cohort study was conducted from 1995 through 2009. Amniotic fluid (AF) samples (n=1,281) were collected at the time of cesarean delivery from women who delivered singleton newborns at term (gestational age ≥38 weeks). Intra-amniotic inflammation was diagnosed if the AF concentration of matrix metalloproteinase-8 (MMP-8) was >23 ng/ml. Funisitis was diagnosed by histologic examination if inflammation was present in the umbilical cord. Results The prevalence of MSAF was 9.2% (118/1,281), and 10.2% (12/118) of neonates exposed to MSAF developed MAS. There were no significant differences in the median gestational age or umbilical cord arterial pH at birth between neonates who developed MAS and those who did not (each p > 0.1). Mothers whose newborns developed MAS had a higher median AF MMP-8 (456.8 ng/ml vs.157.2 ng/ml; p < 0.05). Newborns exposed to intra-amniotic inflammation had a higher rate of MAS than those who were not exposed to intra-amniotic inflammation [13.0% (10/77) vs. 0% (0/32), p = 0.03], as did those exposed to funisitis [31.3% (5/16) vs. 7.3% (6/82), relative risk, 4.3; 95% confidence interval, 1.5–12.3]. Among the 89 newborns for whom both AF and placental histology were available, MAS was more common in patients with both intra-amniotic inflammation and funisitis than in those without intra-amniotic inflammation and funisitis [28.6% (4/14) vs. 0% (0/28), p = 0.009], while the rate of MAS did not show a significant difference between patients with intra-amniotic inflammation alone (without funisitis) and those without intra-amniotic inflammation and funisitis [10.9% (5/46) vs. 0% (0/28)]. Conclusion The combination of intra-amniotic inflammation with fetal systemic inflammation is an important antecedent of MAS. This concept has implications for the understanding of the mechanisms of disease responsible for MAS and for the development of prognostic models and therapeutic interventions for this disorder.

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Role of Meconium and Hypoxia in Meconium Aspiration-Induced Lung Injury in Neonatal Rabbits

Cited by 11 publications

References 17 publications

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Meconium aspiration syndrome: a role for fetal systemic inflammation

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