Involvement of Thromboxane A2 and Prostacyclin in the Early Pulmonary Hypertension after Porcine Meconium Aspiration

Abstract

Severe perinatal aspiration of meconium is frequently complicated by unsuccessful neonatal adaptation with associated pulmonary hypertension. This vascular complication is supposedly related to pulmonary release of vasoconstrictory agents, including metabolites of arachidonic acid. Thus, to investigate the role of prostanoids on these meconium-induced circulatory changes in the lungs, the hemodynamic response to meconium instillation was studied in acetylsalicylic acid-pretreated juvenile pigs. Twelve 10-wk-old pigs with adapted lung circulation received 3 mL/kg of 65 mg/mL human meconium via the endotracheal tube. Six of them were medicated with 10 mg/kg acetylsalicylic acid 30 min before meconium insufflation. Hemodynamic parameters and urinary excretion of stable metabolites of thromboxane A2 and prostacyclin were measured serially for 6 h after the insult. Meconium administration induced a biphasic increase in mean pulmonary artery pressure and pulmonary vascular resistance, and a rapid rise in urinary levels of prostanoid metabolites. Acetylsalicylic acid pretreatment prevented the initial (0-1 h) pulmonary hypertensive response and increase in prostanoid excretion. During the second phase (1-6 h), acetylsalicylic acid did not attenuate the progressive increase in mean pulmonary artery pressure and pulmonary vascular resistance nor did it affect the longitudinal distribution of the pulmonary resistances. Our results thus show that in adapted porcine lungs, arachidonic acid metabolites contribute to the early hypertensive response, but have only minor effects during the second phase vascular hypertension.

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

“…19 The airway narrowing in MAS is caused not only by mechanical obstruction by aspirated meconium, but also by peribronchial edema due to the action of various inflammatory mediators. The release of these mediators, including arachidonic acid metabolic products from activated cells during inflammation, modulates the smooth muscle tone and its responses to contractile mediators, 20,21 and may thus contribute to airway hyperreactivity. Whereas airway inflammation is usually associated with increased in vitro smooth muscle reactivity, 17,22 we tested in vitro airway reactivity in rabbits with meconium aspiration.…”

Meconium Induces Only Localized Inflammatory Lung Injury in Piglets

“…Since the meconium concentration of 65 mg/mL, used in the present study, clinically corresponds to thick meconium in amniotic fluid, and after bilateral instillation induces severe persistent hypoxemia and progressive vascular hypertension in neonatal lungs (22), it is apparent that generalized pulmonary inflammatory reaction unlikely has a significant contribution to the pathogenesis of the clinical MAS. The early period of hypoxemia even after unilateral meconium insufflation may be a reflection of an initial ventilation/perfusion mismatch, frequently associated with pulmonary surge of smooth muscle contracting agents, like thromboxane A 2 , which may increase the resistance of the lung vascular bed and airways (9,22,23).…”

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

“…[3][4][5] Investigators using animal models have shown the presence of inflammatory-induced cell death through apoptotic process in meconium-instilled lungs. 6,7 There is increased interest to better understand complex mechanisms of inducing meconium-induced lung cell apoptosis. The purpose of this paper is to review the literature and better understands the mechanisms of meconium-induced lung injury (MILI).…”