Inflammation in Meconium Aspiration Syndrome: Targets for Pharmacological Modulation

Abstract

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.

Effects of dexamethasone on cardiovascular functions in acute phase in meconium‐injured rabbits

“…In a piglet model of MAS, pretreatment with corticosteroids before meconium instillation decreased the pulmonary artery pressure, pulmonary vascular resistance, and right‐to‐left pulmonary shunts by preventing an increase in the post‐arterial resistance, 11,13 probably via suppressed formation of vasoconstrictor eicosanoids and increased production of vasodilator prostanoids, such as prostacyclin 16 . In newborns with severe MAS, dexamethasone treatment improved lung functions and facilitated weaning from the ventilator 14,15 . In the present study enhanced oxygenation and slightly decreased PaCO 2 were found early after dexamethasone treatment, with maximum effect within the first hour after dexamethasone administration.…”

“…In the present study we found no significant effect of single‐dose dexamethasone on systemic blood pressure, CVP, or right‐to‐left pulmonary shunts compared to the non‐treated meconium‐instilled group in the evaluated time intervals. Similarly, in piglets with MAS, administration of dexamethasone after meconium instillation did not influence the pulmonary artery pressure, pulmonary vascular resistance, stroke volume, MBP or heart rate, when compared to meconium‐instilled non‐treated animals 12–14 …”

“…In meconium‐instilled animals, corticosteroids decreased pulmonary vascular resistance and improved lung function 11–13 . Promising results were demonstrated also in neonates with severe MAS, in whom dexamethasone administration facilitated weaning from the ventilator 14,15 . Wider use of corticosteroids, however, is limited by their adverse effects on cardiovascular function, glycemia, immune system and so on, especially when used for longer times.…”

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

“…This may potentiate the lung injury and inhibit lung surfactant production (Mokra & Mokry, 2007; 2010)…”

Study the association of visfatin in the pathogenesis of meconium stained amniotic fluid in labour

“…anti-cytokine antibodies, inhibitors of complement, inhibitors of angiotensin converting enzyme, anticoagulants, inhibitors of proteolytic enzymes, calcium-channel blockers etc. that may be beneficial in MAS [5].…”