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S N Caritis

Publications and source records attributed to S N Caritis.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effect of oral terbutaline on maternal glucose metabolism and energy expenditure in pregnancy.

OBJECTIVE: Terbutaline, a selective beta2-agonist, is a frequently used tocolytic known to affect maternal metabolism. The purpose of this study was to evaluate the effect of oral terbutaline on maternal glucose metabolism and energy expenditure. STUDY DESIGN: Six healthy pregnant women with normal glucose tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was administered to determine the effects on hepatic glucose production with [6-6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon levels were also obtained. Subjects were randomly assigned to either oral terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were conducted 1 week apart, each subject serving as her own control. RESULTS: In the basal state terbutaline was associated with a trend toward increased basal glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free mass/min, p = 0.23). However, there was a significant increase in basal insulin concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a 28% decrease in insulin sensitivity as measured by the glucose infusion rate during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91 vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml, p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003). Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p = 0.025) or 260 kcal/day with terbutaline. CONCLUSION: Decreased peripheral insulin sensitivity, and to a lesser degree increased endogenous glucose production, may represent the pathophysiology of abnormal glucose tolerance observed in many women treated with oral terbutaline. Common side effects such as tremors and tachycardia experienced by many women on a regimen of terbutaline are consistent with our finding of a significant increase in basal energy expenditure.

Adrenergic beta-Agonists↗
PubMed1998

The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network.

OBJECTIVES: This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. METHODS: From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. RESULTS: The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. CONCLUSIONS: Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks.

Cervix Uteri↗
PubMed1997

The Preterm Prediction Study: association of cesarean delivery with increases in maternal weight and body mass index.

OBJECTIVE: Our purpose was to evaluate whether maternal weight and body mass index measured either before or during pregnancy are associated with an increased risk of cesarean delivery. STUDY DESIGN: Maternal weight and height were prospectively collected on 2929 women in the National Institutes of Health Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and 27- to 31-week maternal weight and height were used to calculate the body mass index, and its contribution to the risk of cesarean delivery was determined. Women with prenatally diagnosed congenital anomalies (n = 89) and pregestational diabetes (n = 31) were excluded from analysis. RESULTS: Univariate analysis of risk factors for cesarean delivery in the 2809 eligible women revealed a decreased risk of cesarean delivery with maternal age < 18 years and multiparity; increased risk of cesarean delivery was noted with maternal age > 35 years and a male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5-pound units) or body mass index (1.0 kg/m2 units) were significantly associated with an increased odds of cesarean delivery (p = 0.0001). Each unit increase in prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable stepwise logistic regression analysis confirmed the association of male fetus, age, nulliparity, and body mass index as significant variables contributing to cesarean delivery risk. CONCLUSIONS: The risk of cesarean delivery is associated with incremental changes in maternal weight and body mass index before and during pregnancy after adjustment for potential confounding factors. Prepregnancy counseling about optimizing maternal weight and monitoring weight gain during pregnancy to decrease the risk of cesarean delivery are supported by this study.

Adolescent↗
PubMed1997

Obstetric determinants of neonatal survival: influence of willingness to perform cesarean delivery on survival of extremely low-birth-weight infants. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants. STUDY DESIGN: In this prospective observational study we evaluated 713 singleton births of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units. Major anomalies, extramural delivery, antepartum stillbirth, induced abortion, and gestational age < 21 weeks were excluded. The obstetrician's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear. Grade 3 and 4 intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity, necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or 120 days, and seizures were considered serious morbidity. Survival without serious morbidity was considered intact survival. Logistic regression was used to evaluate the influence of the approach to obstetric management, adjusted for birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness to perform cesarean delivery was associated with increased likelihood of both survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3). Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26 weeks, however, willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity. Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks, willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age. CONCLUSIONS: The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications. Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity. In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery.

Cesarean Section↗
PubMed1997

The preterm prediction study: patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine how various temporal patterns of fetal fibronectin positivity from 24 to 30 weeks predict subsequent fetal fibronectin test results and spontaneous preterm delivery. STUDY DESIGN: A total of 2929 women had vaginal and cervical fetal fibronectin tests obtained at least once at 24, 26, 28, or 30 weeks, and 1870 women had tests performed at all four gestational ages. Fetal fibronectin values > or = 50 ng/ml were considered positive. Various patterns of positive and negative tests were evaluated for prediction of (1) whether the next fetal fibronectin test would be positive or negative and (2) the percent of women with a spontaneous preterm delivery > or = 4 weeks after the last fetal fibronectin test at < 30, < 32, < 35, and < 37 weeks' gestational age. RESULTS: Women with previous negative test results had only a 3% chance of a subsequent positive test result; however, if the last test result was positive, 29% of the next tests were positive. Of the 1870 women with tests at 24, 26, 28, and 30 weeks, 89% had all negative results, 8.4% had one positive result, 1.8% had two positive results, and 0.8% had three or four positive results. The higher the percent of positive tests at 24 to 26 weeks, at 28 to 30 weeks, or at 24 to 30 weeks, the greater the risk of subsequent spontaneous preterm birth. As an example, the risk of spontaneous preterm birth at < 30 weeks for women with two negative fetal fibronectin test results at 24 and 26 weeks was 0.3% versus 16% for women with two positive results. CONCLUSION: The presence of a positive cervical or vaginal fetal fibronectin test result predicts subsequent positive fetal fibronectin positivity and subsequent spontaneous preterm birth. The greater the percent of positive results, the higher is the risk of spontaneous preterm birth. After a positive test result, two negative results are required before the risk of spontaneous preterm birth returns to baseline.

Cervix Uteri↗
PubMed1996

The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. NICHD Maternal Fetal Medicine Units Network.

OBJECTIVE: To determine the relation between vaginal and upper genital tract infection and cervical-vaginal fetal fibronectin levels. METHODS: We screened 2899 women at ten centers every 2 weeks from 23-24 to 30 weeks' gestation for cervical and vaginal fetal fibronectin. A positive test was defined as a level of at least 50 ng/mL. The relation between a positive test and bacterial vaginosis at 23-24 weeks and clinical or histologic chorioamnionitis at delivery plus neonatal sepsis was determined. RESULTS: Fetal fibronectin was present in 4.0% of cervical and/or vaginal samples at 23-24 weeks and was nearly twice as common in women with bacterial vaginosis. Adjusting for the presence of bacterial vaginosis, race, and parity, women positive for fetal fibronectin were much more likely to have clinical chorioamnionitis (mean +/- standard deviation gestational age 30.6 +/- 4.1 weeks), with an odds ratio of 16.4 and 95% confidence interval of 7.1-37.8, and neonatal sepsis (6.3 and 2.0-20.0, respectively), than those who were fetal fibronectin-negative. A positive cervical fetal fibronectin test was a better predictor of clinical chorioamnionitis and neonatal sepsis than was a vaginal test or a combination of vaginal and cervical tests. Among 40 women who delivered before 32 weeks and had placental histology available for evaluation, ten had a positive cervical and/or vaginal fetal fibronectin test before delivery; all ten had histologic evidence of chorioamnionitis, compared with only 13 of 30 women (43%) who were fetal fibronectin-negative (P = .02). CONCLUSION: Women with bacterial vaginosis were more likely to have a positive fetal fibronectin test than uninfected women. Women with a positive fetal fibronectin test who delivered before 32 weeks' gestation all had evidence of histologic chorioamnionitis. Women positive for fetal fibronectin also had a 16-fold increase in clinical chorioamnionitis and a sixfold increase in neonatal sepsis. There is strong evidence that upper genital tract infection and cervical and/or vaginal fetal fibronectin are closely linked.

Adult↗
PubMed1996

The preterm prediction study: a clinical risk assessment system.

OBJECTIVE: Our aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks' gestation and to determine the predictive value of such a system. STUDY DESIGN: A total of 2929 women were evaluated between 23 and 24 weeks' gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity. RESULTS: A total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index (<19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery (> or = 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women. CONCLUSIONS: Although it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations.

Black People↗
PubMed1996

Contraction inhibition by beta-agonists progressively decreases before labor in the rat myometrium.

OBJECTIVE: This study tested the hypothesis that gestational age and agonist concentration are important determinants of beta-adrenergic-dependent myometrial contraction inhibition. STUDY DESIGN: In vitro concentration-response curves for ritodrine and terbutaline were generated with myometrial strips collected from 21-day-pregnant rats. The in vitro efficacy of ritodrine (0.1 mumol/L) was evaluated in tissue from 15-, 18-, and 21-day animals. Contractile responses were analyzed by computer and normalized to a control potassium response. RESULTS: The degree of the inhibitory effects of both drugs was concentration dependent over the range of 0.01 to 10 mumol/L. The duration of contraction inhibition progressively decreased from 15 to 21 days of pregnancy. CONCLUSION: The degree of tachyphylaxis with beta-agonists is dependent on and increases with the gestational age of the target tissue. beta-Agonist type was not an important determinant of the duration of inhibitory response. We speculate that the effect of gestational age on tachyphylaxis may be related to increased myometrial expression of inactivating beta-adrenergic receptor kinases.

Adrenergic beta-Agonists↗
PubMed1996

The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to determine the association between the presence of bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147 women with twins at 24 and 28 weeks' gestation for more than 50 potential risk factors for spontaneous preterm birth. We also measured cervical length with ultrasound scans and tested for the presence of bacterial vaginosis. Fetal fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation. Outcomes included spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical length < or = 25 mm was more common at both 24 and 28 weeks, a statistically significant difference. There were no significant differences in most other risk factors. Of the factors evaluated by means of univariate analysis at 24 weeks, only a short cervix (< or = 25 mm) was consistently associated with spontaneous preterm birth. The odds ratio and 95% confidence interval for spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3 to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length < or = 25 mm was not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio 46.1; confidence interval, 4.2 to 1381), a positive fetal fibronectin result was significantly associated with spontaneous preterm birth at < 32 weeks. Bacterial vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of twins. Multivariate analysis confirmed the association between cervical length < or = 25 mm at the 24-week visit and spontaneous preterm birth and also confirmed that at 24 weeks the other risk factors were less consistently and often not statistically significantly associated with spontaneous preterm birth. Of the risk factors evaluated at 28 weeks, only a positive fetal fibronectin was associated with a significantly increased risk for spontaneous preterm birth. CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not significantly associated with spontaneous preterm birth of twins. At 24 weeks, cervical length < or = 25 mm was the best predictor of spontaneous preterm birth at < 32 weeks, < 35 weeks, and < 37 weeks. Of the risk factors evaluated at 28 weeks, fetal fibronectin was the only statistically significant predictor of spontaneous preterm birth at < 32 weeks.

Adolescent↗
PubMed1995

Low-dose aspirin in nulliparous women: safety of continuous epidural block and correlation between bleeding time and maternal-neonatal bleeding complications. National Institute of Child Health and Human Developmental Maternal-Fetal Medicine Network.

OBJECTIVE: Our purpose was to determine the frequency and safety of the use of epidural anesthesia and the correlation between bleeding time and maternal-neonatal bleeding complications in a group of pregnant women who participated in a multicenter trial of low-dose aspirin in pregnancy. STUDY DESIGN: Data regarding type of anesthesia used for labor and delivery were available in 1629 nulliparous women who were randomly assigned at 13 to 27 weeks to receive 60 mg/day aspirin or a placebo. A total of 891 (55%) received epidural anesthesia, and the remaining 738 did not. RESULTS: Among the 891 women known to have received epidural anesthesia, 451 were assigned to low-dose aspirin and 440 to placebo. There was no instance of bleeding related to epidural use. In addition, there were no differences in maternal and neonatal complications between those receiving or not receiving epidural anesthesia. Within the group receiving epidural anesthesia there were no differences in bleeding complications between those assigned to aspirin on placebo. One of the five centers also obtained bleeding times in 303 women (149 received aspirin and 154 received placebo). The mean +/- SD bleeding time in women assigned to low-dose aspirin was significantly higher than in women assigned to placebo (6.99 +/- 2.95 minutes vs 5.99 +/- 2.43 minutes, p = 0.004). In addition, the frequency of women having a bleeding time > 10 minutes was higher in the aspirin group (14.1% vs 5.2%, p = 0.01). Interestingly, women who received an epidural anesthetic had a lower bleeding time than those not receiving an epidural (p = 0.003), irrespective of the treatment used. CONCLUSIONS: In women assigned to low-dose aspirin there were no adverse effects related to epidural anesthesia. In spite of an increased bleeding time in a subset of pregnant women assigned to low-dose aspirin, maternal-neonatal bleeding complications were not increased.

Analysis of Variance↗
PubMed1995

Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

OBJECTIVE: We conducted a large clinical trial to evaluate the effect of low-dose aspirin on the frequency of preeclampsia in nulliparous women. A secondary objective of the trial was to identify those clinical characteristics that might be predictive for the development of preeclampsia. STUDY DESIGN: A total of 2947 healthy women with a single fetus were prospectively followed up from randomization at 13 to 27 weeks' gestation to the end of pregnancy. Of these, 1465 women were assigned to low-dose aspirin and 1482 to placebo. Baseline maternal blood pressure and demographic characteristics were examined for the prediction of preeclampsia. RESULTS: Preeclampsia developed in 156 women (5.3%). Four characteristics predicted the development of preeclampsia: in order of importance, systolic blood pressure at entry, prepregnancy obesity (weight as a percentage of desirable weight), number of previous abortions or miscarriages, and smoking history. Contrary to previous reports, black race was not a risk factor for preeclampsia. Systolic blood pressure was a better predictor of preeclampsia than either diastolic or mean arterial blood pressure. The greater the blood pressure or prepregnancy weight, the greater was the risk for preeclampsia. If the woman had never smoked or had never been previously pregnant, her risk was also higher than average. A multivariate logistic regression equation based on these four factors was able to define a tenth of the population at very high risk and another tenth at very low risk; the ratio of risk between these two groups was 12:1. The p value for each of the multivariate coefficients of the risk equation was systolic blood pressure (p < 0.001), prepregnancy weight (p < 0.01), smoking history (p < 0.01), and gravidity (p < 0.05). There were no statistically significant differences in the predictive values of these risk factors between women receiving low-dose aspirin or placebo. CONCLUSIONS: These risk factors should be of value to practitioners counseling women regarding preeclampsia. Moreover, such risk factors should be considered in the design of future studies dealing with preeclampsia.

Abortion, Induced↗
PubMed1994

Nonsurgical management of placenta percreta: a case report.

BACKGROUND: Although placenta percreta is rare, its sequelae include potentially lethal hemorrhage and loss of reproductive function. Therapy directed toward control of life-threatening hemorrhage frequently includes emergency hysterectomy. CASE: A woman with placenta percreta, suspected clinically and documented radiographically, was treated nonsurgically. Following delivery, the placenta was left in situ and methotrexate chemotherapy was initiated to aid destruction of the trophoblastic tissue. Eight months later, hysteroscopy showed a normal uterine cavity with only a small area of calcification at the presumed implantation site. Two years later, the patient had a normal pregnancy and vaginal delivery. CONCLUSION: Placenta percreta can be managed with preservation of the uterus, but careful follow-up may be required until the entire placenta has resorbed.

Adult↗
PubMed1993

Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known. METHODS: We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity. RESULTS: Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01). CONCLUSIONS: Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.

Abruptio Placentae↗
PubMed1991

Comparison of pulsatile and continuous ritodrine administration: effects on uterine contractility and beta-adrenergic receptor cascade.

In this study we compare the uterine contractility and beta-adrenergic receptor effects of identical doses of ritodrine administered intermittently or continuously for 24 hours in pregnant sheep. Ritodrine was administered intravenously to five animals as a pulse, 16 micrograms/kg every 1.5 hours, whereas five other animals received ritodrine as a continuous infusion of 0.18 microgram/kg/min. Ritodrine plasma concentrations at steady state were comparable in both groups and averaged 18 ng/ml. Animals receiving ritodrine pulses demonstrated no alteration of myometrial beta-adrenergic receptors or adenylyl cyclase activity, and ritodrine inhibited oxytocin-induced contractility comparably at 4 and 24 hours. Animals receiving ritodrine continuously had a significant decrease in myometrial beta-adrenergic receptors and adenylyl cyclase activity, yet ritodrine inhibition of oxytocin-induced uterine contractility was sustained for 24 hours. Oxytocin receptors were not affected by ritodrine administration and were similar in both groups. At the dose studied, oxytocin-induced contractions are comparably inhibited by ritodrine for 24 hours whether the drug is given continuously or in a pulsatile fashion.

Adenylyl Cyclases↗
PubMed1991

Changes in uterine venous prostaglandin F metabolites following intravenous infusion of ritodrine in sheep.

The effectiveness of the beta-adrenergic receptor agonist ritodrine as a tocolytic agent is limited by the tachyphylaxis that occurs with its sustained usage. In order to understand the nature of this tachyphylaxis, we investigated the effect of ritodrine on uteroplacental prostaglandin (PG)F2 alpha production in pregnant sheep. Using general anesthesia in five pregnant sheep, we placed catheters in the aorta and vena cava and in the uterine vein from the uterine horn. In random order on different days, we infused ritodrine (4 micrograms/kg/minute) or physiologic saline into the maternal vena cava at a rate of 0.184 mL/minute. Uterine venous and maternal arterial blood was sampled 60 minutes before and immediately before the infusion and then at 60, 120, 180, and 240 minutes during the infusion. After centrifugation, the serum was frozen and then assayed for the metabolite of PGF2 alpha (PGFM). Uterine venous PGFM increased significantly after 60 minutes of ritodrine infusion (mean increase 1.164 ng/mL; P less than .05), and this increase was sustained during the 4-hour infusion. The PGFM gradient across the uteroplacental bed (uterine vein - aorta) was also significantly elevated during the infusion, suggesting a uteroplacental or fetal membrane source of the PG. Saline had no effect on uterine venous PGFM or the PGFM gradient. These results suggest that ritodrine stimulates PGF2 alpha production, and this may contribute to the tachyphylaxis that occurs with ritodrine and limits its long-term effectiveness as a tocolytic agent.

Animals↗