The effects of a non-selective and cyclooxygenase II selective inhibitor on prostacyclin and thromboxane production by placental arteries

THE FIRST TRIMESTER YARIV YOGEV, ODED LANGER, AVI BEN HAROUSH, ORLI MOST, RONY CHEN, MOSHE HOD, St. Luke’s-Roosevelt Hospital Center, University Hospital of Columbia University, Obstetrics and Gynecology, NY, New York, Rabin Medical Center, Perinatal Division, Department of Obstetrics and Gynecology, Petach-Tikva, Israel, Israel OBJECTIVE: In diabetic women, hyperglycemia during the first trimester is associated with an increased rate of congenital malformations and spontaneous abortion. However, there is a lack of data concerning the ambulatory normal glycemic profile in non-diabetic subjects. Therefore, we investigated the glucose characteristics defining normoglycemia during the first trimester. STUDY DESIGN:Daily glycemic profile was evaluated during the first trimester in 42 non-diabetic non obese gravid patients using Continuous Glucose Monitoring System-CGMS. CGMS measures glucose levels every 5 minutes for 72 consecutive hours for a total of 288 measurements daily. All women were asked to refrain from any lifestyle modification or dietary restriction during the study period. RESULTS: (1) Overall, averages of 774 G 41glucose measurements were recorded for each woman. (2) Average gestational age was 8.1 G 2.4 weeks and mean BMI was 24.1 G 1.4 kg/m. (3) For the total 126 days (42 women ! 3 days) of continuous glucose monitoring glycemic characterization revealed a daily mean glucose level of 79.3 G 7 mg/dL, mean fasting glucose of 74.5 G 11 mg/dL, and a mean preprandial glucose level of 77.6 G 9 mg/dL. (4) Further analysis was performed in relation to meals. The 1-h postprandial glucose peak value was 108.7 G 16.9 mg/dL and the time interval required to reach this peak value was 65.4 G 28 minutes. (5) During study period, no hypoglycemic events (glucose !40 mg/dL) were identified. CONCLUSION: Our data provides a definition of normoglycemia in early pregnancy in non-obese, non-diabetic women. This in turn may be used as a measure in the first trimester to evaluate the degree of deviation from this standard that may be associated with adverse outcome in a diabetic pregnancy. 474 THE EFFECTS OF A NON-SELECTIVE AND CYCLOOXYGENASE II SELECTIVE INHIBITOR ON PROSTACYCLIN AND THROMBOXANE PRODUCTION BY PLACENTAL ARTERIES DAMIAN PAONESSA, ANDREA SHIELDS, JAMES WRIGHT, BOBBY HOWARD, PETER NAPOLITANO, Madigan Army Medical Center, tacoma, Washington, MAMC, Clinical Investigation, tacoma, Washington OBJECTIVE: To determine if there is a difference in the production of thromboxane and prostacyclin by placental arteries treated with a non-selective cyclooxygenase or a cyclooxygenase II selective inhibitor. STUDY DESIGN: Four arteries were obtained from each of 8 placentas collected from normal parturients. Specimens were incubated in Dulbecco’s modified eagle media containing one of the following: (1) ibuprofen, (2) celecoxib, (3) indomethacin at therapeutic serum concentrations, or (4) Dulbecco’s for control. Culture media samples were obtained at 2, 4, 6, 12, 24 and 48 hours. Serial samples were then assayed for thromboxane and prostacyclin by immunoassay of their stable metabolites. Statistical analysis was performed using analysis of variance, all values are reported as mean concentration (ng/mg tissue) G SD. RESULTS: Compared to controls, thromboxane production was decreased at 4 hours in the indomethacin arm (0.25 G 0.09 vs. 0.57 G 0.30) P ! .05, at 6 hours in the ibuprofen arm (0.27 G 0.19 vs. 0.63 G 0.35) P ! .05 and at 48 hours in the celecoxib arm (0.70 G 0.34 vs. 1.033 G 0.47) P ! .05. Compared to the celecoxib arm, thromboxane production was significantly lower in both the indomethacin (0.29 G 0.086 vs. 0.70 G 0.34) P ! .01 and ibuprofen arm (0.26 G 0.14 vs. 0.70 G 0.34) P ! .01 at 48 hours. Prostacyclin production was significantly decreased at 24 hours in the indomethacin (0.48 G 0.30 vs. control 1.89 G 1.28) P ! .05 and ibuprofen arm (0.51 G 0.47 vs. control 1.89 G 1.28) P ! .05 compared to controls. There was no difference in prostacyclin production in the celecoxib arm compared to controls. CONCLUSION: Exposure to indomethacin and ibuprofen rapidly and dramatically inhibits the production of thromboxane by placental arteries within 6 hours. Exposure to celecoxib decreases thromboxane production of placental arteries after 24 hours, but the effect is less than indomethacin and ibuprofen at 48 hours.