Jeffrey Lipshitz

Phencyclidine: Its transfer across the placenta as well as into breast milk

Phencyclidine (PCP) is a dangerous and unpredictable drug which is widely abused among young people. Acute placental transfer of this drug was studied in pregnant rabbits and mice where it was shown to cross the placenta readily. Rabbit fetal levels of radioactivity reached their peak 2 hours after parenteral administration of PCP to the doe. In the mouse, where actual PCP levels were determined, there was a tenfold higher concentration of PCP in fetal tissue than in maternal blood. In lactating mice, the drug was found to cross rapidly into breast milk where it reached concentrations which were 10 times that of plasma. As PCP may be teratogenic and has been shown to be harmful to the infant during the postnatal period, those treating pregnant women should be aware to these possible routes of exposure for the developing infant and should counsel their patients accordingly.

Cardiac output and uteroplacental blood flow in diet-restricted and diet-repleted pregnant rats

Cardiac output and uteroplacental blood flow were measured with 15 mu radioactive microspheres in anesthetized pregnant rats which were fed: (1) ad libitum throughout gestation; (2) a 50% restricted diet from day 5 of gestation; and (3) a 50% restricted diet from days 5 to 13 of gestation and ad libitum from day 14 of gestation. An additional group of nonpregnant rats fed ad libitum was also used. Dietary restriction caused a net maternal weight loss and a 20% reduction in mean fetal weight and mean placental weight by day 21 of gestation. Restricted dams fed ad libitum during the last week of gestation showed a net maternal weight gain, while mean fetal weight, but not placental weight, was near that of the ad libitum--fed controls. In the diet-restricted rats, total cardiac output was reduced 30% relative to controls by days 20 and 21 of gestation, but cardiac output per unit maternal body weight was not significantly different. Dietary restriction decreased both total uterine and placental blood flow by about 65%. Diet repletion late in gestation did not significantly increase total cardiac output or cardiac output per unit body weight. Total uterine and placental blood flows were near those of controls, primarily because of an increased fraction of cardiac output distributed to the uterus.

The effect of hydralazine on placental perfusion in the spontaneously hypertensive rat

Intravenous hydralazine was administered to 16 spontaneously hypertensive rats on day 21 of gestation. The radioactive labeled microsphere technique was used to assess the change in organ perfusion produced by the drug. Vascular resistance to most organs was decreased, except to the placentas, stomach, and cecum, where it increased by 43%, 104%, and 44%, respectively. Blood flow to the organs was redistributed, and although it was increased to the lungs, kidneys, liver, and adrenals, it was significantly reduced to the spleen, stomach, placentas, cecum, large intestine, and pancreas. The effect of hydralazine on placental perfusion was opposite to the effect on the uterus (myometrium). Patients with the highest blood pressures tend to have the poorest placental perfusion. Intravenous hydralazine should be used cautiously in these patients.

Placental transfer of intravenous fluoride in the pregnant ewe

Fluoride ion is produced with the biotransformation of two commonly used anesthetics, methoxyflurane and enflurane. Fluoride ion is added to prenatal vitamin preparations and water to prevent carious teeth. Very high levels of fluoride assailure. Previous studies of placental transfer of fluoride ion were conflicting. Our study in pregnant ewes revealed rapid transfer of the fluoride ion across the placenta with high fetal to maternal ratios as early as 1 minute.

Placental transfer of 14C-hexoprenaline

The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.

Effect of hexoprenaline on uteroplacental blood flow in the pregnant rat

The effect of beta-adrenergic agonists on uteroplacental blood flow is controversial. Human studies, with the use of indirect methods to assess uteroplacental blood flow, show conflicting results. Animal studies in the near-term pregnant sheep model have the disadvantages that the sheep has a syndesmochorial placenta and that the uteroplacental vessels are thought to be maximally dilated near term. The effect of hexoprenaline, a new beta 2-sympathomimetic drug, was assessed in the awake pregnant rat on day 14 of gestation by means of the radionuclide-labeled microsphere method. Hexoprenaline increased placental blood flow by 198% and distribution of cardiac output to the placentas by 229%. Renal blood flow was reduced by 24%. Saline solution administration produced no significant effects.

Effects of hexoprenaline on the lecithin/sphingomyelin ratio and pressure-volume relationships in fetal rabbits

A placebo-controlled, double-blind trial was carried out on 74 New Zealand White rabbit fetuses from 15 does to assess the effect of a fetal injection of hexoprenaline on surfactant release. After the uterus was exposed, half the fetuses received 0.1 ml (0.25 microgram) of hexoprenaline injected intraperitoneally through the intact uterine wall; the other half received an equivalent volume of placebo. After 3 hours, the abdomen was reopened, and the fetuses were surgically delivered and killed before breathing. The lecithin/sphingomyelin (L/S) ratios, obtained from lung washings, revealed a mean of 1.59:1 for the placebo group and 1.92:1 for the hexoprenaline group (p less than 0.001). Pressure/volume curves were generated from the lungs of 24 fetuses from 10 does, and the volume of air in the lungs for each pressure was analyzed in four ways: total volume, volume per gram of fetal body weight, volume per gram of dry lung weight, and as a percentage of total lung capacity at a pressure of 40 cm H2O. A first and second inflation-deflation curve was obtained for each experiment. The lungs from the hexoprenaline-treated group retained significantly more air than those from the placebo group. The most significant comparison was obtained when lung volume was expressed per gram of dry lung weight. The possibility of administering a beta 2-sympathomimetic drug to the mother in advanced preterm labor, specifically to release surfactant in the fetal lung, is suggested.

Effect of long-term administration of β2-sympathomimetic drug in the diet-restricted pregnant rat model

To assess whether the maternal-fetal balance could be altered in favor of the fetus during malnutrition by increasing uteroplacental blood flow, 0.5 mg of hexoprenaline per day was added to the diet of one group of diet-restricted rats, while another group served as controls. The radionuclide-labeled microsphere method was used to determine blood flow to the maternal placentas and other organs. Maternal carcass weight but not fetal or placental weights were increased in the hexoprenaline-fed rats. Blood flow to the ileum, jejunum, hepatic artery, kidneys, and placentas was significantly greater in the hexoprenaline group compared with those rats fed the restricted diet alone. Although the placental blood flow was increased in the hexoprenaline-fed rats, the supply of nutrients remained restricted, and in the mother the inherent maternal-fetal balance was maintained by an increase in the blood flow to the liver and small intestine.

Evaluation of the Corometrics 315 telemetry system for fetal monitoring

The Corometrics 315 telemetry system is a commercially available unit which can transmit both fetal heart rate (FHR) and intrauterine or external pressure data to a standard fetal monitor. This system was evaluated in 40 patients, ten of whom were monitored simultaneously by telemetry and direct-wire fetal monitoring. Because of some differences in electronic engineering between the telemetry and direct fetal monitoring systems, the following differences were found: Comparison of the simultaneously obtained FHR recordings revealed that the telemetry system rejected most of the motion artifacts while maintaining true variability. There were no differences as regards readability, FHR, and beat-to-beat variability. The intrauterine pressure values were the same, although the telemetry system gave a smoother waveform with less motion artifact. The main advantages of the telemetry system were found to be: (1) The patient was free to move about and ambulate during labor. (2) It was possible to obtain uninterrupted monitoring while the patient was moved from the labor room to the delivery room and throughout the second stage of labor.