INVOLVEMENT OF THROMBOXANE A(2) AND PROSTACYCLIN IN THE EARLY PULMONARY-HYPERTENSION AFTER PORCINE MECONIUM ASPIRATION

Severe perinatal aspiration of meconium is frequently complicated by u nsuccessful neonatal adaptation with associated pulmonary hypertension . This vascular complication is supposedly related to pulmonary releas e of vasoconstrictory agents, including metabolites of arachidonic aci d. Thus, to investigate the role of prostanoids on these meconium-indu ced circulatory changes in the lungs, the hemodynamic response to meco nium instillation was studied in acetylsalicylic acid-pretreated juven ile 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 A(2) and prostacyclin were measured serially for 6 h after the insult. Meconium administration induced a biphasic increase in mean pulmonary artery pressure and pulmonary vasc ular resistance, and a rapid rise in urinary levels of prostanoid meta bolites. Acetylsalicylic acid pretreatment prevented the initial (0-1 h) pulmonary hypertensive response and increase in prostanoid excretio n. During the second phase (1-6 h), acetylsalicylic acid did not atten uate the progressive increase in mean pulmonary artery pressure and pu lmonary vascular resistance nor did it affect the longitudinal distrib ution of the pulmonary resistances. Our results thus show that in adap ted porcine lungs, arachidonic acid metabolites contribute to the earl y hypertensive response, but have only minor effects during the second phase vascular hypertension.