Fetal Venous Samples Research Articles

Placental transfer of enfuvirtide in the ex vivo human placenta perfusion model

The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon). Human cotyledons were perfused for 90 minutes in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine. Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide. Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.

The pharmacokinetics of glyceryl trinitrate with the use of the in vitro term human placental perfusion setup

Objective: The purpose of this study was to determine the pharmacokinetics of glyceryl trinitrate across the in vitro term human perfused placenta. Study Design: Peripheral placental lobules (n = 6) were dually perfused. The maternal side was perfused with glyceryl trinitrate (100 nmol/L) for 90 minutes. Serial samples from the fetal venous and maternal venous catheters were collected and assayed for glyceryl trinitrate and its vasoactive metabolites (1,2- and 1,3-glyceryl dinitrate) with gas chromatography. Fetal arterial perfusion pressure was continuously measured throughout. Data are expressed as the mean ± SEM, with 1-way analysis of variance followed by a Newman-Keuls post-hoc test (P <.05). Results: The mean steady-state fetal venous:maternal side ratio of glyceryl trinitrate concentration was 18.5% ± 3.7%. The 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate levels in the fetal venous samples and maternal venous samples were less than the lower end of the sensitivity range of the assay (<5 nmol/L). Fetal arterial perfusion pressure did not change with glyceryl trinitrate administration. Conclusion: The glyceryl trinitrate in the fetal venous sample was approximately 18.5% of the glyceryl trinitrate in the maternal side in this preparation. The presence of glyceryl dinitrates in the maternal venous samples and the fetal venous samples indicates the capacity for placental biotransformation of glyceryl trinitrate. The data demonstrate that glyceryl trinitrate, at a tocolytic concentration, has the ability to cross the placenta but was not found to affect fetal arterial perfusion pressure. (Am J Obstet Gynecol 2002;187:187-90.)

Absence of Placental Transfer of Pentasaccharide (Fondaparinux, Arixtra®) in the Dually Perfused Human Cotyledon in vitro

The synthetic pentasaccharide, fondaparinux, is the first of a new antithrombotic class: selective factor Xa inhibitors. Comparative clinical trials of fondaparinux versus heparins in prevention and treatment of venous thromboembolism are ongoing. Little is known about fondaparinux during pregnancy, as women of child-bearing potential were excluded from clinical trials. No particular safety issue, for either mother or fetus, has been reported for heparins. The objective of this study was to compare in vitro the steady state placental transfer of fondaparinux and enoxaparin at the plasma concentrations reached during acute treatment of venous thromboembolism (1.75 microg/mL and 1 anti-Xa IU/mL respectively), using antipyrine (20 mg/L) as reference. No biological activity was detectable in the fetal venous effluent during perfusion of enoxaparin-antipyrine, fondaparinux-antipyrine or control media. Furthermore, fetal venous samples did not differ significantly from fetal arterial samples. This apparent absence of placental transfer supports further evaluation of fondaparinux in pregnant women.

Plasma and placental calcitonin gene-related peptide in pregnancies complicated by severe preeclampsia

OBJECTIVE: Our purpose was to determine the concentration of calcitonin gene-related peptide, a potent vasodilator, in maternal plasma, fetal plasma, and placental tissue from pregnancies complicated by severe preeclampsia. STUDY DESIGN: The following groups were studied: severe preelcmapsia (group 1, n = 21), normal pregnancies matched for mode of delivery (group 2, n = 21), and nonpregnant women (group 3, n = 17). Maternal venous blood samples were drawn before labor, and fetal venous samples were drawn from the chorionic plate immediately after delivery. Calcitonin gene-relted peptide was also quantified in placental tissue samples from 15 patients in group 1 and 15 patients in group 2. Calcitonin gene-related peptide was measured with a sensitive and specific radioimmunoassay. RESULTS: No differences were found between maternal plasma calcitonin gene-related peptide concentrations in groups 1 and 2 (29.8 ± 4.2 and 30.4 ± 4.3 pmol/L, respectively). Both had levels similar to those in group 3 (28.5 ± 5.4 pmol/L). Maternal plasma concentrations in the preeclamptic group were unchanged 3 days post partum (29.1 ± 3.6 pmol/L). Fetal plasma calcitonin gene-related peptide concentrations were similar in groups 1 and 2 (30.2 ± 3.9 and 32.2 ± 8.8 pmol/L, respectively). A significant correlation was found between maternal and fetal calcitonin gene-related peptide concentrations ( r = 0.43, p < 0.01). Like plasma levels, calcitonin gene-related peptide levels in the supernatants of placental extracts were not different in preeclamptic and normal pregnancies (108.0 ± 70.4 and 100.9 ± 56.1 fmol/gm, respectively). CONCLUSION: On the basis of plasma and placental concentrations, calcitonin gene-related peptide does not seem to play an important role in the pathophysiologic mechanisms of preeclampsia.

Placental monoamine oxidase content and inhibition: Effect of enzyme inhibition on maternofetal transfer of noradrenaline (norepinephrine) in the human placenta in vitro

The effect of monoamine oxidase (MAO) inhibition on maternofetal transfer of noradrenaline (NA) has been investigated in vitro using dual perfusion of isolated human placental lobules. As a first step, placental MAO content and its sensitivity to inhibition by pargyline were assessed in incubation studies of homogenates as well as during perfusion, taking rat liver as reference. Our results show that the human placenta, though it contains as great an enzyme activity as rat liver, was less sensitive to inhibition by pargyline than the latter. MAO inhibition by pargyline significantly reduced the NA clearance from maternal to fetal circulation. Thus the proportion of unmetabolized NA radioactivity in fetal venous samples decreased significantly after pargyline treatment. A concomitant rise in the proportion of mainly O-methylated metabolites was also observed. We speculate that the apparent activation of catechol-O-methyl transferase pathway, observed in our studies on MAO inhibition, may play an important role in limiting NA transfer towards the fetus in toxaemic pregnancies associated with the reduction in placental MAO.