Studies of circulation and acid-base balance in pregnant sheep: I. The effect of aminophylline infusion

The maternal and fetal effects of aminophylline on hemodynamics and acid-base and blood gas balances were evaluated by 11 infusions to four chronically catheterized sheep at 114-142 days' gestation. Maternal and fetal arterial blood samples were drawn for baseline determination at 15-minute intervals. Mean maternal and fetal pH levels and heart rates increased significantly. Respiratory alkalosis was indicated by a concomitant fall in mean maternal carbon dioxide pressure. We conclude that aminophylline infusion (5.6 mg/kg of body weight/15 min) to pregnant sheep may cause maternal and fetal tachycardia and alkalosis, with a possible increase in uterine blood flow, but no changes in fetal blood gas status or blood pressure.     

Intrapartum repetitive maternal heart rate deceleration pattern simulating nonreassuring fetal status

Uterine contraction-associated accelerations of the maternal heart rate are considered to reflect both a transient contraction-related increase in cardiac output and endogenous catecholamine secretion. Uterine contraction-associated decelerations of the maternal heart rate are rare and remain unexplained. A young multiparous patient with systemic lupus erythematosus (postrenal transplant for lupus nephropathy-related renal failure) presented in early labor at 39 weeks gestation, prior to elective repeat cesarean section. Intrapartum continuous maternal heart rate monitoring demonstrated repetitive uterine contraction associated decelerations of the maternal heart rate of 60 beats per minute, each lasting 2 minutes, simulating nonreassuring fetal status. Simultaneously depicted fetal heart rate was reassuring. This case demonstrates an unusual marked early intrapartum affect of uterine contractions upon the maternal heart rate. In addition, this case illustrates the potentially dangerous similarity of an intrapartum maternal heart rate to an abnormal fetal heart rate pattern, and emphasizes the importance of correct identification of the maternal and fetal heart rates, respectively.     

Maternal Serum Human Placental Growth Hormone (hPGH) at 11 to 13 Weeks of Gestation in Preeclampsia

Objective. Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11–13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Methods. The maternal serum concentration of hPGH at 11–13 weeks was measured in a case–control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. Results. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. Conclusion. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.     

利托君抑制宫缩时孕妇心率变化的初步研究

目的探讨利托君抑制宫缩时孕妇心率的变化与治疗的关系。方法选择先兆早产孕妇110例。将利托君100mg加入5％葡萄糖溶液500mL中静脉滴注,从6滴(每分钟)开始,根据疗效调整药物剂量,待宫缩消失后维持40～48小时或更长,以后改口服,病情反复者可重复用药。比较用药前后孕妇心率的变化及与药物剂量的关系,并分析分娩时间、胎儿重量和Apgar评分等指标。结果孕妇基础心率与孕周之间呈较典型的先升后降的变化趋势。静滴利托君至宫缩停止时,孕妇心率明显增加(P＜0.01),但不同孕周之间的心率无显著差异(P＞0.05)。随着利托君用药剂量的增加,孕妇心率呈剂量依赖性升高,最高峰不超过140/min。用药后孕妇分娩时间明显延长(P＜0.01),其中单纯先兆早产者延长最多(P＜0.05)。胎儿平均体重(2.42±0.49)kg,平均Apgar评分≥8分。结论在抑制宫缩治疗中利托君介导的孕妇心率增加可作为评价药物疗效的指标之一。     

Comparison of maternal mortality and morbidity between trial of labor and elective cesarean section among women with previous cesarean delivery

OBJECTIVE: This study was undertaken to assess the safety of trial of labor after previous cesarean delivery. STUDY DESIGN: Retrospective cohort study of 308,755 Canadian women with previous cesarean delivery between 1988 and 2000. Occurrences of in-hospital maternal death, uterine rupture, and other severe maternal morbidity were compared between women with a trial of labor and those with an elective cesarean section. RESULTS: Rates of uterine rupture (0.65%), transfusion (0.19%), and hysterectomy (0.10%) were significantly higher in the trial-of-labor group. Maternal in-hospital death rate, however, was lower in the trial-of-labor group (1.6 per 100,000) than in the elective cesarean section group (5.6 per 100,000). The association between trial of labor and uterine rupture was stronger in low volume (<500) than in high volume (> or =500 births per year) obstetric units. CONCLUSION: Trial of labor is associated with increased risk of uterine rupture, but elective cesarean section may increase the risk of maternal death.     

The effects of aminophylline and nifedipine on contractility of isolated pregnant human myometrium

To characterize the effects of aminophylline and nifedipine on pregnant human myometrium, in vitro contractility studies were performed on myometrial strips obtained at cesarean section. The strips were stimulated with oxytocin (800 mU/L) to simulate labor and then were exposed to increasing concentrations of aminophylline (40, 100, and 400 mumol/L) or nifedipine (5, 10, and 20 micrograms/L). Both drugs produced a dose-related decrease in contraction strength, as measured by the time-integrated force of contraction. Aminophylline lengthened the period of contraction in a manner that was not dose dependent. Low-dose nifedipine (5 micrograms/L) increased the period of contraction, but higher doses had no effect on frequency. Both drugs produced a net reduction in the effectiveness of labor, as measured by the average force (time-integrated force divided by period). These results indicate that both aminophylline and nifedipine may be clinically useful tocolytic agents.     

The comparative actions of uterine inhibiting drugs in the pregnant rat

Studies were made to determine the effect of various contraction-inhibitors against spontaneous uterine contraction in rats during late pregnancy. 1) The duration and rate of inhibitory activity differed from inhibitor to inhibitor, showing dose-response relationship. As a result of this investigation of the changes in the intensity and frequency for 17 inhibitors, Ca-blocker, beta 2-stimulants and dibutyryl c-AMP had the strongest effects, PG-antagonist, and the anti-inflammatory drugs such as aminophylline were much weaker in their inhibitory activity. 2) When the progress of uterine inhibition was investigated on the basis of quantitative changes of PG and c-AMP in bath medium, it was found that both PGE1 and PGF2 alpha were significantly reduced after administration of terbutaline and indomethacin, c-AMP decreased significantly after administration of PGE1 analogue, oxytocin and PGF2 alpha. The c-AMP levels increased significantly after administration of terbutaline and verapamil. These were no significant changes in c-AMP levels when indomethacin and aminophylline were used. During the administration of the uterine inhibitors, c-AMP increased significantly both in vivo and in vitro. Therefore, c-AMP may be regarded as an important parameter indicating the degree of inhibition of contraction.     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.     

Spinal anesthesia and ephedrine in pregnant monkeys

A study of the maternal and fetal effects of spinal hypotension and its treatment with ephedrine was made in 6 pregnant monkeys whose activity was controlled with succinylcholine and nitrous oxide. During spinal hypotension, mean maternal arterial blood pressure decreased 54 per cent; cardiac output, 18 per cent; total peripheral resistance, 47 per cent; and uterine blood flow, 30 per cent. Fetal PO₂ decreased from a mean of 27.1 ± 6.4 to 15.4 ± 7.8. Fetal pH decreased from a mean of 7.34 ± 0.04 to 7.22 ± 0.05, and fetal PCO₂ increased from 41.6 ± 6.1 to 50.9 ± 10.4 mm. Hg. Ephedrine was effective in restoring these changes in the maternal cardiovascular system toward prespinal levels and preventing further deterioration of the fetus.     

The effects of maternal caffeine and chocolate intake on fetal heart rate

Objective: The aim of our study was to analyze the effects of caffeine and chocolate (70% cocoa) on fetal heart rate (FHR). Study design: Fifty pregnant women with uncomplicated gestation, matched for age and parity, underwent computerized FHR recording before and after the consumption of caffeine and then, after one week, before and after 70% cocoa chocolate intake. Computerized cardiotocography (cCTG) parameters were expressed as mean and SD. The differences were tested for statistical significance using the paired t-test, with significance at p?<?0.05. Results: The number of uterine contraction peaks, the number of small and large accelerations (10 and 15 beats per minute for 15 seconds), the duration of episodes of high variation and the short-term FHR variation were significantly higher (p?<?0.001) after maternal coffee intake. The number of large accelerations, the duration of episodes of high variation and the short-term FHR variation were significantly higher (p?<?0.001) after maternal consumption of chocolate, whilst no effect of cocoa was found during contractions. Conclusions: Our results suggest that maternal intake of both caffeine and 70% cocoa have a stimulating action on fetal reactivity. This finding is likely due to the pharmacological action of theobromine, a methilxanthine present in coffee and in chocolate. The correlation between maternal caffeine intake and increased uterine contraction peaks is likely due to the effect of caffeine on the uterine muscle.     

Changes in arterial uterine blood flow velocity waveform during uterine contraction and relaxation in labor

The arterial uterine blood flow velocity waveform during uterine contraction and relaxation in labor was measured with ultrasonic continuous wave (CW) Doppler device in 44 pregnant women at 37-41 weeks of gestation. The fetal heart rate (FHR) was also recorded by cardiotocogram during labor in every case. 1. Both the resistance index (RI) and pulsatility index (PI) of the arterial uterine blood flow velocity waveform were significantly higher during uterine contraction than during relaxation (p less than 0.005). These increases in RI and PI during contraction were not influenced by the maternal heart rate. The reverse or interrupted end-diastolic flow was demonstrated in 16.3% of the cases. 2. No abnormal FHR patterns were observed in any of the cases except two with early deceleration or mild variable deceleration in which uterine arterial end-diastolic flow was maintained. The fetal conditions did not seem to be influenced by the reduction of arterial uterine blood flow in our study.     

The role of trophoblast binucleate cells in implantation in the goat: a quantitative study

The number of goat trophoblastic binucleate cells, the incidence of their migration and the formation of trinucleate and syncytial cells in the maternal uterine epithelial layer was estimated quantitatively using transmission electron microscopy between 14 and 23 days postcoitum (dpc). Binucleate cells were first observed at 18 dpc and their proportions increased rapidly from less than 1 per cent to 16 per cent by 19 dpc and 22 per cent by 23 dpc. The appearance of trinucleate cells within the maternal uterine epithelial layer coincided with evidence of migration and fusion of binucleate cells with individual uterine epithelial cells, and an increased death rate among the other uninucleate uterine epithelial cells. There was also a slight increase in the incidence of intraepithelial lymphocytes close to the trinucleate cells. The quantitative studies uphold the hypothesis that at implantation in the goat, placental trinucleate cells and their subsequent multinucleate syncytial plaque derivatives are fetomaternal hybrid tissue formed by fusion of a binucleate cell(s) with a single uterine epithelial cell.     

Late decelerations and brain tolerance of the fetal monkey to intrapartum asphyxia.

Eight monkey fetuses near term were subjected to regulated asphyxia during labor by mechanically constricting the maternal abdominal aorta and diminishing blood flow to the uterus. A magnitude of asphyxia was produced and maintained for an initial three hours that was close to but not sufficient to elicit late decelerations. The asphyxia was then augmented during a fourth hour to cause late decelerations of magnitudes of 5 to 15 per cent of the initial heart rate. After termination of the fourth hour of asphyxia, the fetuses were delivered by hysterotomy and provided intensive care. During the three to nine months of survival after birth, all animals were neurologically intact; on necropsy the brains were free of pathologic changes both grossly and microscopically. These results support the thesis that fetal heart rate monitoring during labor exhibits a sensitivity sufficient to diagnose asphyxia of the fetus of clinical significance before it reaches a magnitude that may cause permanent neurological injury. The results are particularly pertinent to those clinical circumstances where the decreases in intervillous space blood flow brought about by uterine contractions are accentuated due to low maternal blood pressure.     

Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade.

Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.     

The effect of aminophylline on uterine smooth muscle contractility and prostaglandin production in the pregnant rat uterus in vitro

The effect of aminophylline on contractility and prostaglandin production was investigated in a 20-day pregnant rat uterus preparation in vitro. A significant decrease was observed in frequency (24.4% of control, p less than 0.05) and contractile force (13.8% of control, p less than 0.001) in rat uterine segments treated with aminophylline. Treated segments produced more prostaglandin E2 (139.6% of control, p less than 0.001) and less prostaglandin F2 alpha (73.8% of control, p less than 0.001) during the 45-minute observation period. No significant difference in thromboxane B2 or 6-ketoprostaglandin F1 alpha production was noted. This is the first observation of prostaglandin levels in rat uterine segments treated with aminophylline. It could not be concluded from this study whether the observed changes in prostaglandin production are directly related to the relaxant effect of aminophylline.     

Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine

Previous studies in pregnant ewes have demonstrated that intravenous (IV) cocaine produces increased maternal blood pressure and vasoconstriction of the uterine arteries, resulting in decreased uterine blood flow and decreased fetal oxygen levels. To determine whether these responses to cocaine were mediated by alpha 1-adrenergic receptor stimulation, cocaine was administered to four pregnant ewes before and after phenoxybenzamine hydrochloride, an alpha 1 receptor antagonist. Before phenoxybenzamine infusion, cocaine 2.0 mg/kg produced a 53% increase in maternal mean arterial pressure (MAP), a 50% reduction in total uterine blood flow, and a 191% increase in uterine vascular resistance. Cocaine also increased fetal MAP by 24%, increased the fetal heart rate (FHR) by 51%, and reduced fetal PO2 by 29%. Alpha 1 receptor blockade after phenoxybenzamine 5.0 mg/kg was confirmed by a lack of change in uterine blood flow to IV norepinephrine 30 micrograms before cocaine administration. After phenoxybenzamine, cocaine produced no increase in maternal or fetal MAP. However, total uterine blood flow decreased 44%, uterine vascular resistance increased 59%, FHR increased 36%, and fetal PO2 fell 18%. Because the fetal responses mimicked the maternal responses to cocaine both before and after phenoxybenzamine, phenoxybenzamine apparently crossed the placenta to block fetal alpha 1 receptors as well. Alpha 1-adrenergic receptor stimulation is the major mechanism for the maternal and fetal hypertensive responses to cocaine. Although cocaine produces uterine artery vasoconstriction primarily by alpha 1 adrenergic receptor stimulation, its vasoconstrictive effects may involve other vasoactive neurotransmitters, such as dopamine or serotonin.     

The relation between plasma unconjugated oestriol and cystine aminopeptidase concentrations and uterine contractions.

The relation between maternal plasma unconjugated oestriol (E3) concentrations and uterine activity was investigated by very frequent, carefully timed determinations of E3 during synchronously recorded uterine contractions in six normal subjects. There was an initial rise (10 to 50 per cent above the mean) in E3 levels reaching a peak coincident with the contraction peak (range 20 seconds before to 15 seconds after) followed by a fall of similar magnitude below the mean reaching a nadir about 80 seconds (range 60 to 105 seconds) after the contraction peak. Although the pattern of E3 fluctuation was most marked in labour the overall degree of variation was no greater than at other times. Cystine aminopeptidase (CAP) concentrations in the same serum samples showed no significant correlation with uterine contractions. The reasons for, and practical applications of, the E3 results are discussed.     

The effect of berotec (Th 1165a) on spontaneous and induced uterine activity in the pregnant baboon.

Berotec (Th 1165a), a specific beta-adrenergic agent, has been found to be a more potent agent than metaproterenol in the inhibition of uterine activity in animals and human beings. The effect of berotec on spontaneous (postinduced) and induced uterine activity in the pregnant baboon near term was investigated. Berotec administered intravenously in a dose of 5 mug per minute consistently and significantly reduced spontaneous uterine activity as well as uterine activity by either oxytocin or prostaglandin F2-alpha. The frequency of contractions was consistently reduced whereas the effect on the amplitude of contractions was less marked. There was no reduction of the baseline muscle tonus. Berotec infusion produced a marked increase in the maternal heart rate, averaging 40 beats per minute. Berotec appears to be a potent inhibitor of spontaneous, oxytocin-induced, and prostaglandin-induced uterine activity in the pregnant baboon, but it has considerable cardiovascular side effects.     

Characteristics of uterine activity during the breast stimulation stress test

Characteristics of uterine activity produced by nipple stimulation were studied in 185 consecutive breast stimulation stress tests. Adequate contractions were produced in 95.6% of tests. Exaggerated uterine response (contractions occurring more than once every two minutes or lasting more than 90 seconds) was present in 45.5% of the patients. Twenty-one percent of the patients with such uterine activity also had a fetal heart rate (FHR) deceleration (hyperstimulation breast stimulation stress test), without adverse fetal outcome. The time in minutes from start of nipple stimulation to the first contraction (stimulation contraction interval) was recorded for each patient. Significant difference was not observed in the stimulation contraction interval distribution between the groups with and without exaggerated uterine activity. The authors conclude that there is a relatively high incidence of exaggerated uterine activity response to the breast stimulation stress test and that close surveillance of mother and fetus is warranted during antepartum nipple stimulation.     

Intervillous space during uterine contractions in human subjects: an ultrasonic study.

Six patients at term were examined by ultrasound during uterine contractions. The length, thickness, and surface of the placental area were found to increase during uterine contraction compared to relaxation. The conclusion is drawn that during uterine contractions the intervillous space is distended. During uterine contraction more maternal blood is available for exchange with the fetal compartment.