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Biomedical subjects

J C Dumas

Publications and source records attributed to J C Dumas.

At least 19 recordsLinked to original sources

Influence of maternal blood flow on the placental transfer of three opioids--fentanyl, alfentanil, sufentanil.

The placental transfer of three opioids used in peridural analgesia, fentanyl, alfentanil and sufentanil, and two reference substances, antipyrine and *H2O, was determined ex vivo in the human placental cotyledon system. (1) In the first set of experiments, the infusion rates were constant and fixed at physiological flow rates. Under these conditions, the magnitude of the materno-fetal transfer was in the following order: *H2O = antipyrine = fentanyl > alfentanil > sufentanil. No particular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, the influence of different flow rates, reflecting various pathophysiological conditions, was examined. There was a linear relationship between the maternal flow and the materno-fetal transfer of the three opioids. On the other hand, for antipyrine and tritiated water, the relationship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was observed for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the maternal flow and the materno-fetal transfer. (4) These findings emphasize the importance of the lipophilic and hydrophilic characteristics of drugs on placental transfer, especially in the event of fluctuations in maternal flow.

Alfentanil

Experimental study of transplacental passage of alpha interferon by two assay techniques.

Two methods of assaying alpha interferon (IFN-alpha) were compared during an experiment aimed at determining whether IFN-alpha crosses the human placenta. Human placentas, collected after delivery following a normal pregnancy to term, were catheterized on both sides: fetal and maternal. The IFN-alpha was introduced in known amounts in the maternal circulation and was assayed in the efferent fetal fluid. The following two detection methods were used: radioimmunoassay by competition with [125I]IFN-alpha and assay with a biological system in which IFN-alpha protected Madin-Darby bovine kidney cells from destruction by vesicular stomatitis virus. The results obtained by the two methods were in perfect agreement for the efferent fetal fluid samples. They showed the absence of placental transfer of IFN-alpha. The biological method was found to be more sensitive than radioimmunoassay for low IFN-alpha titers (< 10 IU/ml) but was less reproducible, probably owing to the use of twofold dilutions. The specificities of the two methods were similar and their practicalities were equivalent; the biological method, however, was less costly. The study illustrates the complementarity of the two methods, which were based on different principles. The agreement obtained between the two methods provides a clear confirmation of the experimental results.

Adult

Placental transfer of glycosaminoglycans in the human perfused placental cotyledon model.

Placental transfer of unfractionated heparin (UH), of low molecular weight heparin CY 216 (LMWH) and of Dermatan sulphate (DS) was studied using the human perfused placental cotyledon model. Two different techniques were used to assess the transfer: labelled molecules and biological activities as measured by antifactor Xa or antifactor IIa activities. No biological activity was present in the fetal circulation, for any of the drugs used; however, very low fractions of the perfused radioactivity were recorded, 0.76% +/- 0.36%, 1.46% +/- 1.44% and 2.37% +/- 0.89% for DS, UH and LMWH, respectively.

Dermatan Sulfate

Maternal and umbilical cord concentrations of fentanyl after epidural analgesia for cesarean section.

The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.

Analgesia, Epidural

Effects of pH on antipyrine transfer across the human placenta ex vivo.

The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.

Adult

[Changes in water metabolism in rats under the influence of naloxone: role of vasopressin].

The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals.

Animals

Effects of addition of nitrogen during rapid compression of baboons.

A series of dives was carried out to depths of 600 and 800 m seawater (msw) using baboons (Papio papio). Experiments were designed to study the effects of compression and the use of a He-N2-O2 gas mixture on high-pressure nervous syndrome (HPNS). When N2 was added to the He-O2 mixture at the beginning of a linear compression (200 msw/h), the symptoms associated with HPNS were still seen; in addition, the electroencephalogram (EEG) changes were more severe than those seen without N2. By use of an identical mixture, a 2-h exponential compression to 600 msw produced less severe signs of HPNS than the nonexponential profile. By use of a 2-h exponential compression to 600 msw and with addition of N2 at the end of compression, the HPNS that had been started under the He-O2 mixture decreased. Progressive addition of N2 during compression reduced the behavioral signs of HPNS without further EEG changes. These results show that the action of N2 is more complex than can be explained by a simple narcotic pressure antagonism and that the HPNS differed according to the gas mixture used.

Animals