Urinary excretion of prostacyclin and thromboxane metabolites in threatened preterm labor: effect of indomethacin and nylidrin.
OBJECTIVE
We studied the role of smooth muscle-relaxing prostacyclin and its endogenous antagonist, thromboxane A2, in preterm labor by assessing the urinary output of the breakdown products of prostacyclin (6-keto-prostaglandin F1 alpha and 2,3-dinor-6-keto-prostaglandin F1 alpha) and those of thromboxane A2 (thromboxane B2, 2,3-dinor-thromboxane B2).


METHODS
Thirty-three women in preterm labor between 25 and 34 weeks of gestation were studied before, during, and after treatment with indomethacin (n = 16) or nylidrin (n = 17). Urinary prostanoid levels were determined by high-performance liquid chromatography followed by radioimmunoassay, and the excretion was expressed as nanograms of prostanoids per millimole of creatinine. Statistical analyses were done by paired and unpaired Student t test, by Spearman's correlation, and by Wilcoxon signed-rank test.


RESULTS
Preterm labor was accompanied by a median 32% higher output of prostacyclin and thromboxane A2 metabolites as compared with those in 25 controls. At 8 hours after the start of treatment indomethacin induced maximal drops in 6-keto-prostaglandin F1 alpha (70%), in dinor-6-keto-prostaglandin F1 alpha (60%), in thromboxane B2 (85%), and in dinor-thromboxane B2 (95%) excretion. Within 1 week after the cessation of indomethacin, output of prostacyclin metabolites had recovered to pretreatment values, whereas output of thromboxane A2 metabolites was yet lower than the pretreatment value. Nylidrin induced no change in the output of prostacyclin and thromboxane A2 metabolites.


CONCLUSIONS
Threatened preterm labor is associated with a rise in prostacyclin and thromboxane A2 synthesis. Indomethacin inhibits more thromboxane A2 than does prostacyclin synthesis. These findings may explain the fetal vascular changes during maternal indomethacin treatment.
Kurki
T
T
I Department of Obstetrics and Gynecology, University of Central Hospital of Helsinki, Finland.
Viinikka
L
L
Ylikorkala
O
O
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D011464:Epoprostenol / Q000652:urine*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D007700:Kinetics; D009756:Nylidrin / Q000627:therapeutic use*; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000652:urine*; D011247:Pregnancy; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine*; D015145:Tocolysis
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D009756:Nylidrin; D011464:Epoprostenol; D007213:Indomethacin