G.R. Van Petten

The effects of prolactin on pulmonary maturation in the fetal rabbit

The effect of ovine prolactin administration on the fetal rabbit pulmonary pressure volume relationship was determined. Using pentobarbital anesthesia, on Day 24 of gestation, a midline incision on the maternal abdomen was made to expose the bicornuate uterus. Fetal rabbits in one horn of the uterus were injected intramuscularly with a dose of 1.0 mg (0.05 ml) of prolactin solution. Similarly, fetuses in the opposite horn were administered an equivalent volume of control vehicle. On Day 26 of gestation, no significant enhancement of lung maturation, as judged from the pressure volume relationship, was found to result from prolactin administration. These results suggest that prolactin does not initiate the secretion of surface active material into the alveolar lumen of the fetal lung in sufficient amounts to induce physiologic maturation of the rabbit fetal lung.

Chronic preparation of the pregnant ewe and fetus for pharmacological research: The placental transfer and fetal effects of bunitrolol

Abstract The chronically prepared ovine fetus is a very useful model for the determination of placental transfer and pharmacological effects of drugs. Methods for pre- and post-operative care of pregnant sheep, induction and maintenance of anesthesia, and the surgical approach to the fetus for implantation of ECC leads and cannulas in the femoral artery and saphenous vein are presented and the various problems and pitfalls discussed. Brief descriptions of methods for implanting EEC electrodes, a thermistor, and alternate placement of cannulas in the carotid artery and jugular vein are included. As an example of the use which may be made of this model for fetal pharmacology, the effects of maternal administration of the β-adrenoceptor antagonist, bunitrolol (Ko 1366), in the pregnant ewe and fetus are described. Bunitrolol exhibited partial agonist activity, as evidenced by an increase in heart rate, in both the ewe and fetus and also significantly inhibited the response of isoproterenol on both the maternal and fetal heart. Since both the partial agonist activity and β-adrenoceptor antagonist action occurred in the fetus very quickly (

Cardiovascular effects of fever in the ewe and fetal lamb

Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewes temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function.

The effects of dopamine on blood pressure and heart rate of the unanesthetized fetal lamb

The effects of dopamine on blood pressure and heart rate have been studied in continuously cannulated fetal lambs and adult sheep. Drugs were administered by direct intravenous injection into either the fetus or the adult sheep, and blood pressure was measured from an arterial cannula and heart rate was computed from the electrocardiogram (ECG). The magnitude of the fetal pressor response to dopamine increased slightly as the dose of dopamine (1, 10, 50, 100, and 200 mcg. per kilogram was increased, but the magnitude of the response did not increase with advancing gestation (112 to 145 days). However, in the adult sheep, the dose-response relationship was much steeper. In both cases the pressor response was accompanied by a reflex bradycardia that was blocked by atropine (1 mg. per kilogram). In the atropinized fetus, doses of 50 to 200 mcg. per kilogram of dopamine produced tachycardia (30 to 120 b.p.m) and a greater pressor response than that in the unatropinized fetus. Thus, the fetal cardiovascular system is capable of responding to relatively large amounts of dopamine injected as a bolus, suggesting that relatively large amounts of endogenous dopamine would have to be secreted by the mast cells to significantly alter fetal cardiovascular function.

The effects of NA872 on pulmonary maturation in the fetal lamb and rabbit

The effect of fetal administration of NA872, metabolite VIII of Bisolvon, on the lecithin/sphingomyelin (L/S) ratio of ovine tracheal fluid and of its administration to the pregnant doe on the fetal rabbit pulmonary pressure-volume relationship was determined. Intravenous administration of NA872 in the long-term cannulated lamb fetus in a dose of 4 mg. per day from either 120 to 125 or 125 to 130 days of gestation produced a significant increase in the L/S ratio. Administration of 4 mg. per kilogram per day to the pregnant doe on days 21 to 24 of gestation resulted in significant enhancement of lung maturation in the 25 day fetal rabbit lung as judged from the pressure-volume relationship; a smaller dose, or the same total dose given over shorter time periods, had no significant effect in the 25 day rabbit fetus. Similarly, 8 mg. per kilogram given to the doe on days 26 and 27 produced no over-all significant effect on the 28 day rabbit fetus, although a seasonal effect was found at this age.

The inhibition and reactivation of human maternal and fetal plasma cholinesterase following exposure to the organophosphate, dichlorvos☆

Abstract Spontaneous and chemically-induced reactivation of organophosphate-inhibited cholinesterase were studied using as an enzyme source plasma obtained from non-pregnant females, pregnant females at term and their respective neonates, sampled immediately following delivery. Aliquots of plasma were incubated with dichlorvos (10−6M) for 5 min at 37°C resulting in a 96 percent inhibition of cholinesterase activity in all three groups at which time either pralidoxime chloride (10−3M) or an equivalent volume of saline was added to the reaction flask and the restoration of cholinesterase activity was monitored over the next 120 min. Pralidoxime-mediated cholinesterase reactivation in ‘non-pregnancy’ plasma was significantly greater than that observed in either ‘maternal’ or ‘fetal’ plasma, however, no significant difference was noted in reactivation rates for these latter two groups. Significant differences were also observed in the rates of spontaneous reactivation, however, after correcting for this, there were still significant differences in the rates of pralidoxime-mediated reactivation (non-pregnant > pregnant ≥ fetal).

Characterization of maternal and fetal ovine plasma cholinesterase

Abstract Cholinesterase of maternal and fetal ovine plasma, obtained at 112–115 days of gestation, has been characterized and compared by using various techniques including statistical evaluation of kinetic parameters when using acetyl-, propionyl-, and butyrylthiocholine, gel filtration, polyacrylamide-gel electrophoresis, and sensitivity to various inhibitors. Hydrolysis of acetylthiocholine, the optimum substrate, was found to be two to three times faster in fetal plasma than in maternal plasma, although the Michaelis constants did not differ. In both maternal and fetal plasma, gel filtration yielded a major and a minor peak of cholinesterase activity, whereas electrophoresis yielded six bands of activity, including three major bands. These findings suggested quantitative rather than qualitative differences between the maternal and fetal activity. Despite the quantitative differences, there was no difference in the maternal and fetal cholinesterase sensitivity to inhibition by eserine, diisopropylfluorophosphate, and dichlorvos.

A Maternal-fetal comparison of ovine plasma esterases☆

Abstract The esterases of maternal and fetal ovine plasma were characterized and compared early in the third trimester of gestation. Various techniques were used including statistical evaluation of kinetic parameters, gel-filtration and sensitivity to various activators and inhibitors. Maternal esterase activity, expressed in terms of p-nitrophenyl acetate hydrolysis, was found to be 8-fold higher than fetal activity and although both arylesterase and aliesterase appeared to be present in fetal plasma, their contribution to the total activity was relatively small.

Plasma Esterase Development in the Perinatal Lamb

Ovine plasma cholinesterase and nonspecific esterase activities were determined during the last 45 days of fetal development and first 48 h of extrauterine life and compared to adult activities. Marked differences in the development pattern of these enzymes were found. Fetal plasma cholinesterase activity increased between 102 and 112 days gestation to approximately twice adult values and thereafter progressively decreased to adult levels at 48 h postpartum. In contrast, fetal nonspecific esterase activity at 102 days gestation was only about 8% of the adult activity; a steady increase in this activity was found from 102 days gestation to term. From term to 48 h postpartum there was a marked increase of nonspecific esterase activity but the activity at 48 h was still only about 25% of the adult value.