Involvement of thromboxane A2 and prostacyclin in the early pulmonary hypertension after porcine meconium aspiration.
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.
Soukka
H
H
Department of Pediatrics, University of Turku, Finland.
Viinikka
L
L
Kääpä
P
P
D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome / Q000150:complications* / Q000503:physiopathology*; D010547:Persistent Fetal Circulation Syndrome / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D013552:Swine; D013928:Thromboxane A2 / Q000502:physiology*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D013928:Thromboxane A2; D011464:Epoprostenol; D001241:Aspirin