The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS)

Wu, Jing‐Ming; Yeh, Tsu F.; Wang, Jiu-Yao; Wang, Jieh N.; Lin, Yuh Jyh; Hsieh, Wu Shiun; Lin, Ching‐Hsuan

doi:10.1002/(sici)1099-0496(1999)27:18+<205::aid-ppul66>3.0.co;2-0

Cited by 37 publications

(24 citation statements)

References 10 publications

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“…The mediators playing a primary role in lung vascular injury are TNF , IL-1 , PAF, ET-1, TXA 2 , leukotrienes, and products of complement activation, while the secondary mediators may include neutrophil-derived proteinases and oxygen radicals [45]. Increased levels of vasoconstrictors -thromboxanes [21], leukotrienes [24], prostaglandins, and ET-1 [25] appear hand in hand with increased pulmonary artery pressure and vascular resistance after meconium instillation. Moreover, bile acids of meconium may directly induce pulmonary vasoconstriction [55].…”

Section: Vasomotoric Changes In Masmentioning

confidence: 81%

“…While leukotrienes LTC 4 , LTD 4 , and LTE 4 are referred as slowreacting substance of anaphylaxis (SRS-A), LTB 4 is a potent chemotactic agent synthetized by alveolar macrophages and neutrophils. In piglets with MAS, higher levels of 6-ketoPGF 1 , LTC 4 and LTD 4 in the tracheal aspirate than in controls were found, but without clear correlation between cytokines and elevation of pulmonary artery pressure [24].…”

Section: Arachidonic Acid Metabolitesmentioning

confidence: 98%

“…Furthermore, dexamethasone alleviated meconium-induced airway hyperresponsiveness to histamine associated with lung inflammation [59]. In newborns with MAS, intravenous dexamethasone decreased number of leukocytes in tracheal aspirate [126] and levels of several cytokines, and improved lung functions and facilitated weaning from the ventilator [127,128].…”

Section: Corticosteroidsmentioning

confidence: 99%

“…It seems that changes associated with meconium aspiration become severe very early and there is only limited chance to overcome on-going inflammatory response. However, two-dose dexamethasone treatment enhanced gas exchange and reduced oxygen requirements in piglets [127]. Similarly in newborns with MAS, dexamethasone given for several days in a reducing schedule significantly improved lung functions and facilitated weaning from the ventilator [128].…”

Section: Corticosteroidsmentioning

confidence: 99%

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Inflammation in Meconium Aspiration Syndrome: Targets for Pharmacological Modulation

Mokrá¹,

Mokrý

2007

CPR

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Pathophysiology of meconium aspiration syndrome (MAS) is complex and interactions between individual pathomechanisms are still not completely understood. As recently shown, inflammation plays a significant role in the pathogenesis of MAS. Activated cells release and stimulate production of a wide variety of mediators, including cytokines, enzymes, reactive species, and other biologically active substances in meconium-injured lungs. Anti-inflammatory drugs acting on different levels of inflammatory cascade may in combination with other treatment (exogenous surfactant, inhaled NO, liquid ventilation) improve the clinical status of newborns with MAS. For example, corticosteroids modulate activity of phospholipase A 2 and induced NO synthase, influence migration and activation of leukocytes, and reduce lung edema. Cyclooxygenase inhibitors modulate production of thromboxane and prostaglandins. Phosphodiesterase inhibitors have vasodilating, bronchodilating and anti-inflammatory effects. Antioxidants diminish formation of reactive species. However, there are many other drugs., e.g. anti-cytokine antibodies, inhibitors of complement, inhibitors of angiotensinconverting enzyme, anticoagulants, inhibitors of proteolytic enzymes, calcium-channel blockers etc. that may be beneficial in MAS. Nevertheless, further testing is necessary until the novel approaches may be recommended. In this article, authors reviewed main factors participating in meconium-induced inflammation and pointed out some targets for its pharmacological modulation.

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Section: Vasomotoric Changes In Masmentioning

confidence: 81%

Section: Arachidonic Acid Metabolitesmentioning

confidence: 98%

Section: Corticosteroidsmentioning

confidence: 99%

Section: Corticosteroidsmentioning

confidence: 99%

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Inflammation in Meconium Aspiration Syndrome: Targets for Pharmacological Modulation

Mokrá¹,

Mokrý

2007

CPR

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“…In MAS, indomethacin inhibited release of TXA 2 from epithelial cells (30), but did not influence an expression of COX-2 or iNOS in the lungs (16). On the other hand, pretreatment with acetylsalicylic acid prevented the initial pulmonary hypertensive response and reduced release of prostanoids in piglets with meconium aspiration (13). However, these results are insufficient to recommend COX inhibitors for MAS treatment at the moment, although their adverse effect profile (especially of COX-2 selective inhibitors) is more convenient compared to that in GCs.…”

Section: Inhibitors Of Cyclooxygenasementioning

confidence: 99%

Anti-Inflammatory Drugs in the Treatment of Meconium Aspiration Syndrome

Mokrá

Mokrý²,

Čalkovská³

2011

Acta Medica Martiniana

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Meconium aspiration syndrome (MAS) is a major cause of respiratory distress in both the term and postterm neonates. Obstruction of the airways, dysfunction of pulmonary surfactant, inflammation, lung edema, pulmonary vasoconstriction and bronchoconstriction participate in the pathogenesis of this disorder. Since the inflammatory changes associated with meconium aspiration cause a severe impairment of the lung parenchyma including surfactant and influence the reactivity of both vascular and airway smooth muscle, administration of anti-inflammatory drugs may be of benefit also in the management of MAS. This article reviews effects of various anti-inflammatory drugs used in experimental models of MAS as well as in the treatment of newborns with meconium aspiration. Meconium aspiration syndrome (MAS)MAS is a serious disease in both the term and post-term newborns. Obstruction of the airways by aspirated meconium with subsequent alveolar atelectasis behind the plug and air-trapping, inactivation of pulmonary surfactant, inflammation, edema, pulmonary vasoconstriction are often leading to persistent pulmonary hypertension (PPHN), and bronchoconstriction participate in the pathogenesis of MAS (Figure 1). Because meconium-induced inflammation with its multiple impacts on the lungs plays more important role than was previously thought, various anti-inflammatory drugs have been tested in the treatment of MAS. This article reviews inflammatory changes in MAS as a rationale for anti-inflammatory treatment and introduces anti-inflammatory drugs mostly used in the treatment of MAS. Fig. 1. Scheme of pathomechanisms participating in MAS. A d d r e s s f o r c o r r e s p o n d e n c e :

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