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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- PGI2:
-
prostacyclin
- 6-keto-PGF1α:
-
6-keto-prostaglandin F1α
- TxA2:
-
thromboxane A2
- TxB2:
-
thromboxane B2
- MPAP:
-
mean pulmonary artery pressure
- PVR:
-
pulmonary vascular resistance
- ASA:
-
acetylsalicylic acid
- FIO2:
-
fractional concentration of inspired oxygen
- PaO2:
-
partial pressure of arterial O2
- PaCO2:
-
partial pressure of arterial CO2
References
Tyler DC, Murphy J, Cheney FW 1978 Mechanical and chemical damage to lung tissue caused by meconium aspiration. Pediatrics 62: 454–459
Davey AM, Becker JD, Davis JM 1993 Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. Pediatr Pulmonol 16: 101–108
Ziegler JW, Ivy DD, Kinsella JP, Abman SH 1995 The role of nitric oxide, endothelin, and prostaglandins in the transition of the pulmonary circulation. Clin Perinatol 22: 387–403
Davidson D 1988 Pulmonary hemodynamics at birth: effect of acute cyclooxygenase inhibition in lambs. J Appl Physiol 64: 1676–1682
Abman SH, Stenmark KR 1992 Changes in lung eicosanoid content during normal and abnormal transition in perinatal lambs. Am J Physiol 262: L214–L222
Halushka P, Lefer A 1987 Thromboxane-A2 in health and disease. Fed Proc 46: 131–132
Bui KC, Hammerman C, Hirschl R, Snedecor SM, Cheng KJ, Chan L, Short BL, Bartlett RH 1991 Plasma prostanoids in neonatal extracorporeal membrane oxygenation. Influence of meconium aspiration. J Thorac Cardiovasc Surg 101: 612–617
Dobyns EL, Wescott JY, Kennaugh JM, Ross MN, Stenmark KR 1994 Eicosanoids decrease with successful extracorporeal membrane oxygenation therapy in neonatal pulmonary hypertension. Am J Respir Crit Care Med 149: 873–880
Fujishima S, Aikawa N 1995 Neutrophil-mediated tissue injury and its modulation. Int Care Med 21: 277–285
Soukka H, Rautanen M, Halkola L, Kero P, Kääpä P 1997 Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs. Pediatr Pulmonol 23: 205–211
Runkle B, Goldberg RN, Streitfeld MM, Clark MR, Buron E, Setzer ES, Bancalari E 1984 Cardiovascular changes in group G streptococcal sepsis in the piglet: response to indomethacin and relationship to prostacyclin and thromboxane A2 . Pediatr Res 18: 874–878
Truog WE, Sorensen GK, Standaert TA, Redding GJ 1986 Effects of the thromboxane synthetase inhibitor, dazmemegrel (UK 38,485), on pulmonary gas exchange and hemodynamics in neonatal sepsis. Pediatr Res 20: 481–486
Chelucci GL, Boncinelli S, Marsili M, Lorenzi P, Allegra A, Linden M, Chelucci A, Merciai V, Cresci F, Rostagno C, Gensini GF, Lockhart A, Milic-Emili J 1993 Aspirin effect on early and late changes in acute lung injury in sheep. Intensive Care Med 19: 13–21
Hakim TS 1991 Criteria for analysis of arterial and venous occlusion. J Appl Physiol 70: 665–675
Ylikorkala O, Pekonen F, Viinikka L 1987 Renal prostacyclin and thromboxane in normotensive and pre-eclamptic pregnant women and their infants. J Clin Endocrinol Metab 63: 1307–1312
Tulppala M, Viinikka L, Ylikorkala O 1991 Thromboxane dominance and prostacyclin deficiency in habitual abortion. Lancet 337: 879–881
Roberts JD, Shaul PW 1993 Advances in the treatment of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am 40: 983–1004
Tran N, Lowe C, Sivieri EM, Shaffer TH 1980 Sequential effects of acute meconium obstruction on pulmonary function. Pediatr Res 14: 34–38
Ogletree ML, Brigham KL 1982 Effects of cyclooxygenase inhibitors on pulmonary vascular responses to endotoxin in unanesthetized sheep. Prostaglandins Leukot Med 8: 489–502
Rojas J, Larsson LE, Ogletree ML, Brigham KL, Stahlman MT 1983 Effects of cyclooxygenase inhibition on the response to group B streptococcal toxin in sheep. Pediatr Res 17: 107–110
Yoshimura K, Tod ML, Pier KG, Rubin LJ 1989 Role of vasoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs. J Appl Physiol 66: 929–935
Metz C, Sibbald WJ 1991 Anti-inflammatory therapy for acute lung injury. Chest 100: 1110–1119
Leeman M 1991 The pulmonary circulation in acute lung injury: a review of some recent advances. Intensive Care Med 17: 254–260
Author information
Authors and Affiliations
Additional information
Supported by the Foundation for Pediatric Research, Finland (H.S.), the Finnish Cultural Foundation (H.S.), the Turku University Foundation (H.S.), Jalmari and Rauha Ahokas Foundation (P.K.), and the Finnish Heart Association (P.K.).
Rights and permissions
About this article
Cite this article
Soukka, H., Viinikka, L. & Kääpä, P. Involvement of Thromboxane A2 and Prostacyclin in the Early Pulmonary Hypertension after Porcine Meconium Aspiration. Pediatr Res 44, 838–842 (1998). https://doi.org/10.1203/00006450-199812000-00003
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199812000-00003
This article is cited by
-
Thromboxane promotes smooth muscle phenotype commitment but not remodeling of hypoxic neonatal pulmonary artery
Fibrogenesis & Tissue Repair (2015)
-
Glucocorticoids in the treatment of neonatal meconium aspiration syndrome
European Journal of Pediatrics (2011)
-
Studies of meconium-induced lung injury: inflammatory cytokine expression and apoptosis
Journal of Perinatology (2008)
