Urinary Excretion Rates of 6-Keto-PGF1α, in Preterm Infants Recovering from Respiratory Distress with and without Patent Ductus Arteriosus

Abstract

Summaryvreterm infants have not led to conclusive results (2. 8. 15). This Patency of the ductus arteriosus in preterm infants is mediated by vasodilating prostanoids; however, reliable methods to monitor prostanoid activity or production in preterm infants are lacking. We measured the excretion rates of major and characteristic urinary metabolites of prostacyclin (PG12), PGEl, and PGE2, 6-keto-PGF1,, and 7cr-hydroxy-5,ll-diketotetranorprostane-1,16-dioic acid (PGE-M), respectively. Besides these parameters which reflect total body prostanoid turnover and production, the urinary levels of PGE2 and PGFz,, the primary prostaglandins, were measured as an index of renal prostanoid synthesis. There were four study groups. One contained 11 thriving preterm infants; a second, six preterm infants with respiratory distress syndrome (RDS); a third, 30 preterm infants with RDS and patent ductus arteriosus (PDA); and a fourth, nine fullterm infants. All infants with RDS required artificial ventilation. There were no significant differences in PGE-M, PGE2, and PGF2, excretion rates among the various groups; however, a significant increase of the 6-keto-PGF,, excretion rates was observed in the groups of infants with RDS and with and without PDA (P < 0.01 and P < 0.02, respectively). Spontaneous (n = 2) or indomethacin-induced (n = 6) closure of PDA was associated with weaning from the respirator and a concomitant drop into the normal and subnormal range of the excretion rates of 6-keto-PGF,, ( P < 0.01) and PGE-M ( P < 0.02).Abbreviations GC-MS, gas chromatography-mass spectrometry PDA, patent ductus arteriosus PG, prostaglandin PGE-M, 7cu-hydroxy-5,ll-diketotetranorprostane-l,16-dioic acid PG12, prostacyclin RDS, respiratory distress syndrome There is increasing evidence that persistent PDA in preterm infants with RDS is mediated by vasodilating prostanoids (4, 18). But it is still a matter of debate whether increased prostanoid production or increased prostanoid sensitivity of ductal tissue is the major cause of PDA persistence in preterm infants with RDS (2, 3). It is not known whether PGIz or PGE,, both vasodilating prostanoids, is the actual mediator of ductal dilation in these infants. Nor is it known which organ or tissue is mainly involved in the production of these prostanoids.Several attempts to assess prostanoid activity by radioimmunologic determinations of PGE2 in the peripheral circulation of is not unexpected due to the numerous drawbacks related to measurements of primary (parent) PGs (1 1). There are four major concerns of this approach. 1) Very low circulating levels of primary PGs are expected because of the very rapid metabolism of these compounds and single blood measurements might easily miss rapid fluctuation of PG release. 2) Primary PGs might be released from platelets and white cells during collection and handling of blood samples. 3) Protein binding of prostanoid in blood and plasma may interfere with several conventional extraction procedures. 4) Radioimmunologic assays of prostanoids may lack the...

Effect of Hypoxia on Renal Prostaglandin E₂ Production in Human and Rat Neonates

“…Prostaglandins may have very important physiological and pathophysiological roles in adaptation in early postnatal periods [1,2]. It is well known from clinical experience that birth asphyxia frequently causes the abnor mal renal function.…”

Urinary Excretion of Prostacyclin Metabolites in Infants Born after Maternal Preeclampsia or with Birth Asphyxia

“…After birth, however, the infant's systemic and/or renal PGH production seems not to be de pressed, as there was no significant differ ence in the 6-keto and 2,3-dinor excretions between infants born to preeclamptic moth ers and control infants. Although these two groups were of different gestational ages, previous studies [12] and our present find ings indicate that prostanoid excretion is not influenced by gestational age per se. PGI2 metabolite excretion may be lower after elec tive cesarean section than after vaginal de livery [13], but although most of the infants in the preeclampsia group were born by elec tive cesarean section (table 1), their excre tion values were not lower than those in the control group.…”

“…Urinary excretion of prostanoid metabolites has previously been expressed on the basis of concentra tion as such [11,13] or in relation to urinary creati nine concentration [19][20][21], or, alternatively, on the basis of amount excreted per unit time as such [22] or in relation to body surface area [10,12,14], Since, in the present study, the infants of preeclamptic mothers were markedly smaller than those in the other groups (table 1), and the excretion of creatinine was highly variable in all groups (table 2), the results are ex pressed as nanograms of prostanoid excreted per hour per 1.73 m2 body surface area [23].…”

“…cyclin (PGI2) appears to contribute to the postnatal decrease of pulmonary vascular re sistance, necessary for opening up the pul monary circulation [3], The balance between PGI2 and its antagonist, thromboxane A2, regulates the interaction between the circu lating platelets and the vascular wall [4], and is supposed to be one of the determining fac tors of pulmonary arterial resistance [1]. In experimental hypoxia, neonatal lung PGI2 production is increased [5], as a result of either hypoxia per se or the mechanical ef-both healthy preterm infants; and healthy fects of ventilation [6], term infants [12], However, the effects of PGI2 production of human newborns has been studied either by measuring the plasma concentration [7,8] or the urinary excretion of its metabolites, 6-keto-prostaglandin F ta (6-keto) and 2,3-dinor-6-ketoprostaglandin F |a (2,3-dinor) [9][10][11][12][13][14], or indirectly by mea suring the production of PGI2 by umbilical arterial preparations in vitro [15][16][17].…”

Prolonged indomethacin treatment in preterm infants with symptomatic patent ductus arteriosus: efficacy, drug level monitoring, and patient selection

“…Apparently, they are the ones who are particularly prone to ductus reopening during prolonged artificial ventilation. There are several experimental and clinical lines of evidence suggesting that the artificially ventilated lung releases vasodilatory prostanoids, which might be responsible for an early relapse after discontinuation of indomethacin treatment [21].…”