thromboxane-b2 and Placenta-Diseases

One of the most significant responses to fetal cardiac bypass is severe placental dysfunction characterized by increased vascular resistance. We tested the hypothesis that fetal cardiac bypass triggers the activation of nuclear factor kappa-B (NF-KB), a major regulator of inflammatory response, and that pharmacologic inhibition of NF-KB activation by pyrrolidine dithiocarbamate alleviates fetal cardiac bypass-induced placental dysfunction.. Fifteen pregnant goats at 120 to 140 days' gestation were equally divided into the control group with a sham procedure of fetal sternotomy and cannulation (CG), the fetal bypass group (FB), and the fetal bypass group with 300 mg pyrrolidine dithiocarbamate before sternotomy (FP). Fetal cardiac bypass was performed for 30 minutes. Umbilical arterial flow rate was measured by ultrasonic flowmeter and placental vascular resistance was calculated. Fetal plasma levels of nitric oxide (NO), endothlin-1 (ET-1), 6-keto-prostaglandin F1α (6-K), thromboxane B(2) (TXB2), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were assayed. IL-6 and TNF-α mRNA were analyzed by real-time polymerase chain reaction. NF-KB activation was evaluated by electrophoretic mobility shift assay.. Placental vascular resistance significantly increased in the FB and FP groups compared with the CG group. Increases in plasma levels of NO were observed in all 3 groups. Plasma levels of ET-1 rose significantly in the FB and FP groups without noticeable difference between them. Plasma levels of 6-K, TXB(2), IL-6, and TNF-α increased significantly in the FB group compared with the CG and FP groups. The transcription levels of IL-6 and TNF-α mRNA in the placental tissues of the FB group were significantly higher than in the FP and CG groups. The amount of activated NF-KB in the placental tissues of the FB group was also significantly higher than that in the FP and CG groups.. Fetal cardiac bypass-induced inflammatory response possibly mediated by NF-KB caused placental dysfunction. Pharmacologic inhibition of NF-KB activation and decrease in the inflammatory response did not alleviate the placental dysfunction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Cardiac Surgical Procedures; Electrophoretic Mobility Shift Assay; Endothelin-1; Female; Fetal Blood; Fetal Heart; Gestational Age; Goats; Inflammation; Inflammation Mediators; Interleukin-6; NF-kappa B; Nitric Oxide; Placenta; Placenta Diseases; Placental Circulation; Pregnancy; Pyrrolidines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thiocarbamates; Thromboxane B2; Tumor Necrosis Factor-alpha; Vascular Resistance

To investigate associations between structural, functional and circulatory placental changes in pregnancies complicated by impaired glucose metabolism.. Umbilical artery (UA) blood flow resistance was measured by Doppler velocimetry in 21 gravidae with diabetes/impaired glucose tolerance (IGT) and 10 healthy gravidae. Umbilical and placental vessel segments were incubated for determination of prostacyclin and thromboxane synthesis, and tissues histologically examined. Non-parametric statistical tests at a two-tailed P<0.05 were used.. Placental lesions were more common in diabetes/IGT and, although not being an uniform finding, in general associated with a higher vascular synthesis of thromboxane and/or lower prostacyclin/thromboxane synthesis ratio. As an exception, ischemic villitis was associated with a higher ratio and higher UA flow resistance.. Placental lesions are associated with an altered vascular prostanoid synthesis in diabetes/IGT, but not until structural signs of ischemia develop is a rise of UA blood flow resistance detected.

Topics: 6-Ketoprostaglandin F1 alpha; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Intolerance; Humans; Infarction; Ischemia; Placenta; Placenta Diseases; Pregnancy; Pregnancy in Diabetics; Thrombosis; Thromboxane B2; Umbilical Arteries; Vascular Resistance

To study the influence of platelet activation and lipid peroxidation in fetal blood on umbilical vascular prostanoid synthesis and placental morphology in diabetic pregnancy.. The concentrations of thromboxane A2 (TxA2) and malondialdehyde (MDA) were determined in umbilical cord plasma in 21 women with diabetes mellitus/impaired glucose tolerance (DM/IGT) and ten healthy women. Segments from the umbilical artery and vein were incubated and prostacyclin (PGI2) and TxA2 metabolites were determined. Prostanoid synthesis was stimulated with calcium ionophore at a second incubation. Histological examination was carried out in samples from the umbilical cord, membranes and placental parenchyma. Non-parametric statistical analysis was used, with a two-tailed p < 0.05 considered statistically significant.. Cord plasma TxA2, but not MDA, was higher among DM/IGT women (p = 0.07). There were indications that cord plasma TxA2, but not MDA, was positively correlated with vascular prostanoid synthesis and synthesis capacity. In the umbilical vein, both the basal and stimulated PGI2 production and the stimulated TxA2 production were lower in the DM/IGT group. Ischemic placental lesions were associated with a high TxA, and a low MDA concentration in cord plasma.. Even in less severe forms of impaired glucose metabolism, disturbances in platelet activation significantly affect both biochemical and morphological vessel wall and tissue functions in the umbilicoplacental unit. This could indicate an abnormal programming of fetal cell functions and designate cases at increased risk of developing cellular and organ damage.

Topics: 6-Ketoprostaglandin F1 alpha; C-Peptide; Embryonic and Fetal Development; Epoprostenol; Female; Fetal Blood; Glucose Intolerance; Glycated Hemoglobin; Humans; Lipid Peroxidation; Malondialdehyde; Placenta; Placenta Diseases; Platelet Activation; Pregnancy; Pregnancy in Diabetics; Thromboxane A2; Thromboxane B2; Umbilical Arteries; Umbilical Veins

The metabolism of arachidonic acid (AA) by caruncular and allantochorionic tissues and its regulation was studied in normal cows (n = 13) and those with retained fetal membranes (RFM; n = 9). Tissues were taken via the vagina about 6 hours postpartum and incubated for 6 hours in minimum essential medium containing tritiated AA alone or in the presence of oxytocin, platelet activating factor (PAF), epidermal growth factor (EGF) or ionophore calcium (A23187). The metabolites of AA were separated by reverse phase-high pressure-liquid chromatography. Tissue concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) and plasma 13,14-dihydro-15-keto-PGF2 alpha (PGFM) concentration were also measured by radioimmunoassay. For caruncular tissue, less thromboxane B2 (TXB2) and more 6-keto prostaglandin F1 alpha (PGIM) was synthesized in tissue from the animals with RFM than in the controls. Oxytocin, PAF, EGF and A23187 increased only PGIM production in the control animals; A23187 also decreased TBX2 synthesis. For the allantochorion, more PGE2, leukotriene B4 (LTB4) and PGIM and less TXB2, PGF2 alpha and hydroxyecosatetranoic acids (HETE) was synthesized in tissue from cows with RFM than from animals that delivered normally. All of the substances used in this study increased PGIM, PGF2 alpha and LTB4 and decreased TXB2 production by the allantochorionic tissue in control animals. The metabolism of AA by the allantochorionic tissue seems quantitatively under hormonal control. The metabolism of AA at the level of both maternal and fetal components of the placenta in cows with RFM differed from that seen in animals that expelled the membranes normally.

Topics: 6-Ketoprostaglandin F1 alpha; Allantois; Animals; Arachidonic Acid; Calcium; Cattle; Chorion; Chromatography, High Pressure Liquid; Dinoprost; Dinoprostone; Epidermal Growth Factor; Female; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Oxytocin; Placenta; Placenta Diseases; Platelet Activating Factor; Pregnancy; Thromboxane B2