Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

Korhonen, Kalle; Soukka, Hanna; Halkola, Lauri; Peuravuori, Heikki; Aho, Heikki; Pulkki, Kari; Kero, Pentti; Kääpä, Pietari

doi:10.1203/01.pdr.0000072784.55140.1e

Cited by 30 publications

(31 citation statements)

References 39 publications

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“…24 However, several studies showed a benefit of corticosteroids in MAS. 13,15,16 Corticosteroids reduce edema formation through diminished endothelial damage and microvascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Alleviates Meconium‐Induced Airway Hyperresponsiveness and Lung Inflammation in Rabbits

Mokrý

Mokrá

Antošová

et al. 2005

Pediatric Pulmonology

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Summary. The effects of dexamethasone on in vitro airway reactivity associated with lung inflammation were investigated in rabbits with meconium aspiration. Oxygen-ventilated adult rabbits received an intratracheal bolus of 4 ml/kg body weight of saline (Sal, n ¼ 4) or human meconium (25 mg/ml). Thirty minutes later, meconium-instilled animals intravenously received 0.5 mg/kg of dexamethasone (Dexa, n ¼ 6), or were left without treatment (Meco, n ¼ 5). The animals were ventilated for a further 5 hr and then sacrificed. The left lungs were lavaged with saline, and the white blood cell (WBC) count was estimated. Tracheal and right-lung tissue strips were placed into organ chambers with Krebs-Henseleit solution. Cumulative doses of histamine (10 À8 -10 À3 mol/l) and acetylcholine (10 À8 -10 À3 mol/l) were added to the chambers, and recordings of contractions were made after a 30-min loading phase with a tension of 4 grams, and another 30-min adaptation phase with a tension of 2 g. Tracheal smooth muscle in vitro reactivity to histamine was higher in the Meco than in the Sal group, and dexamethasone decreased the reactivity compared to the Meco group (P < 0.05). Lung tissue in vitro reactivity to histamine was slightly higher in the Meco than in the Sal group (P > 0.05), and dexamethasone decreased the reactivity compared to both the Meco and Sal groups (P < 0.05). No between-group differences were observed in tracheal or lung in vitro reactivity to acetylcholine (P > 0.05). In the Meco group, blood WBC (P > 0.05) and neutrophil (P < 0.05) counts were lower than in the Sal and Dexa groups. Lung neutrophils and eosinophils were higher in both the Meco and Dexa groups than in the Sal group (P < 0.01). Dexamethasone decreased neutrophils (P < 0.05) compared to the Meco group. Meconium-induced airway hyperreactivity to histamine and lung inflammation were alleviated by dexamethasone.

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Section: Discussionmentioning

confidence: 99%

Dexamethasone Alleviates Meconium‐Induced Airway Hyperresponsiveness and Lung Inflammation in Rabbits

Mokrý

Mokrá

Antošová

et al. 2005

Pediatric Pulmonology

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“…19 Experimental study in piglet model suggests that meconium-induced inflammation is localized in the meconium-contaminated areas of the lungs with no generalized inflammatory injury. 20 Correspondingly, local accumulation of neutrophils and macrophages and production of IL-1b and tumor-necrosis factor-a (TNFa) cytokines have been observed. 2,20 Current experimental data suggests that intrapulmonary accumulation of activated neutrophils, similar to various forms of acute injury in adult lungs 21 could aggravate the hypoxic respiratory failure.…”

Section: Neutrophil Influxmentioning

confidence: 99%

“…20 Correspondingly, local accumulation of neutrophils and macrophages and production of IL-1b and tumor-necrosis factor-a (TNFa) cytokines have been observed. 2,20 Current experimental data suggests that intrapulmonary accumulation of activated neutrophils, similar to various forms of acute injury in adult lungs 21 could aggravate the hypoxic respiratory failure. Myeloperoxidase activity is usually used as an important indicator of neutrophil accumulation.…”

Section: Neutrophil Influxmentioning

confidence: 99%

Studies of meconium-induced lung injury: inflammatory cytokine expression and apoptosis

Vidyasagar

Zagariya

2008

J Perinatol

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To review current literature related to cellular mechanisms of meconiuminduced lung injury (MILI). Review of published experimental in vitro and in vivo MAS studies using human and animal lung cells. We found that meconium induces expression of cytokines and angiotensin II (ANG II)-induced apoptotic process in the lung cells. We postulate that inflammatory cytokines induce ANG II expression, which causes apoptotic cell death after binding to its AT1 receptors. We also demonstrated expression of serpins associated with meconium instillation into the lungs. Serpins are proteins that inhibit cellular proteases and elastases. Expression of serpins may be an attempt to recover lung from these injurious effects. In summary our studies show that whereas meconium induces inflammatory cytokines and subsequent cell apoptosis, the lung cells also try to protect themselves by inducing serpins. The balance of these interactions will determine the residual damage. We believe these new findings are very important in understanding of MILI.

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“…4 In line with this finding, tissue PLA 2 activity and concentration of human pancreatic PLA 2 in the meconium-contaminated lungs are concentration-dependently elevated and correlate directly with the severity of the meconium-induced lung injury. 4,16,17 In these studies, promotion of lung edema formation and neutrophil influx through insufflated human PLA 2 -I, either in soluble form or within meconium, further substantiates the central role of pulmonary PLA 2 -I in the development of lung injury after meconium aspiration. 16,17 High PLA 2 activity in meconium, mainly due to secretory PLA 2 -I, is additionally shown to be associated with decreased surfactant biophysical activity in the affected lungs.…”

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confidence: 53%

Phospholipase A2 in meconium-induced lung injury

Kääpä

Soukka

2008

J Perinatol

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Although the triggering mechanisms of tissue inflammation and injury in meconium-contaminated lungs are still unclear, there is increasing evidence to suggest a central role for phospholipase A 2 's (PLA 2 ). In fact, elevated PLA 2 activities together with high enzyme concentrations, especially the amount of pancreatic (group I) secretory PLA 2 (PLA 2 -I), have been detected in human meconium and in meconium-contaminated lungs. Recent data from our laboratory further indicate that human pancreatic PLA 2 , introduced in high amounts within aspirated particulate meconium, is a potent inducer of lung tissue inflammatory injury. Our finding of elevated human PLA 2 -I concentrations in plasma during the first hours after intratracheal meconium administration in newborn piglets further suggests that intrapulmonary aspiration of meconium could also have systemic inflammatory and injurious effects. This, however, remains to be studied in further detail.

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Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

Cited by 30 publications

References 39 publications

Dexamethasone Alleviates Meconium‐Induced Airway Hyperresponsiveness and Lung Inflammation in Rabbits

Dexamethasone Alleviates Meconium‐Induced Airway Hyperresponsiveness and Lung Inflammation in Rabbits

Studies of meconium-induced lung injury: inflammatory cytokine expression and apoptosis

Phospholipase A2 in meconium-induced lung injury

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