Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus

Moore, Thomas R.; Sorg, Joan; Miller, Laurie W.; Key, Thomas C.; Resnik, Robert

doi:10.1016/s0002-9378(86)80044-8

Cited by 250 publications

(91 citation statements)

References 9 publications

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“…It has been argued that the teratogenic effects of cocaine may be due to its ability to decrease placental blood flow and fetal oxygenation (21,36,37). Although this is possible, our studies with embryo cultures in vitro suggest that cocaine can exert direct fetal toxicity, albeit at concentrations much higher than could have been achieved in vivo at the highest dose of 50 pmol/kg used in our studies.…”

Section: El-bizrimentioning

confidence: 53%

Effects of Cocaine on Rat Embryo Development in Vivo and in Cultures

1991

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ABSTRACT. Intraperitoneal injections of 6.25, 12.5, 25, 50, and 100 pmollkg cocaine into pregnant Sprague-Dawley rats once a day from d 0 to 1 9 of gestation caused a dose-dependent increase in fetal soft tissue malformations, primarily of the genitourinary tract. At 100 pmol/kg, all implants were lost and three of the five animals died after six to seven injections. At 50 and 100 pmollkg but not a t lower doses, cocaine caused a small but significant decrease in body weight and food intake. Cocaine did not affect mean fetal and placental weights, although it increased the number of runts and edematous fetuses, and did not cause skeletal malformations. After intraperitoneal injection of 50 pmol/kg, the plasma tlIz of cocaine was 21 f 5 min and peak plasma concentration (1682 + 260 pmol/mL, measured by HPLC) was achieved in 5-10 min; a lower peak plasma concentration (486 f 103 pmol/mL) was achieved in 20-60 min after S.C. injection. Concentrations of dopamine, epinephrine, and norepinephrine in brains of fetuses or newborn pups ( 4 2 h old) of cocaine (50 pmol/kg)-treated rats were not significantly elevated. Cocaine injections did not affect gestational duration nor the growth pattern and the locomotor activity of offspring. However, three pups born to one cocaine-treated animal died 20 d after birth. Cocaine inhibited the growth of 10.5-d-old embryos in culture in a concentration-dependent manner and was more toxic than procaine. Approximately 80% of cocaine was metabolized during a 48-h period in embryo culture medium. It is concluded that cocaine possesses teratogenic potential that may be partly independent of maternal toxicity. (Pediatr Res 29: 187-190, 1991) Cocaine use by pregnant women has been reported to cause a decrease in fetal body weight (1-9), premature delivery (2), genitourinary abnormalities (10, 1 I), cerebral hemorrhage (12), abruptio placentae (1, 2, 13, 14), behavioral abnormalities (14, 15), ocular complications (16), and so on. In general, animal studies (17-23) have provided support for the clinical data. However, in most animal studies cocaine was administered S.C. or orally (17,18,(20)(21)(22)(23)(24), which would result in a lower peak plasma concentration of a longer duration than would occur after equivalent intraperitoneal (25-27) or i.v. (28) doses. We therefore studied the effects of chronic intraperitoneal injections of cocaine on fetal development. Effects of cocaine on the growth of embryos in culture were studied to find out if cocaine's maternal and fetal toxicity could be dissociated. In view of the reported neurochemical effects of cocaine, especially on the dopaminergic system (29), catecholamine levels in brains of fetuses and newborn pups and locomotor activity of offsprings at 5-7 wk of age were also measured. MATERIALS AND METHODSAnimals. Sprague-Dawley virgin female rats (Charles River, St. Constant, Quebec, Canada) weighing 200-225 g were maintained on a 12-h light-dark schedule and fed ad libitum rat food pellets and tap water. For all in vivo studies, females ...

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Section: El-bizrimentioning

confidence: 53%

Effects of Cocaine on Rat Embryo Development in Vivo and in Cultures

1991

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“…More et al (24) have suggested on the basis of studies in pregnant ewes that decreased intrauterine fetal growth results from intermittent interruption of placental blood flow associated with maternal cocaine abuse. In contrast, we found that birth weights of both control and cocaine fetuses were comparable to reported weights of normal 27-d rabbit fetuses (1 4).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Lung Maturation in Cocaine-Exposed Rabbit Fetuses

et al. 1991

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ABSTRACT. Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected S.C. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl a t 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy a t 27 d. Tracheas were cannulated and a volume-pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min a t each pressure (P) increment of 5 cm HzO. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine-exposed lungs differed from controls as follows: I) wet lung weights were lower (0.79 versus 0.89 g, p < 0.02); 2) opening pressure was lower (P25 versus P35); 3) volume (mL/kg) was higher in treated animals a t each pressure step (p < 0.05); 4) end-deflation volume a t PO was higher (30.4 versus 0.8 mL/kg, p < 0.001); and 5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septa1 walls than controls. We conclude that fetal exposure to cocaine results in increased lung distensibility and stability, induction of low surface tension, and morphologic transformations, each of which is consistent with accelerated lung maturation. The cortisol surge suggests a steroid-mediated mechanism for this effect. A pharmacologic effect of cocaine is prevention of norepinephrine reuptake from synaptic spaces. It is also reported that cocaine mediates release of catecholamines from the adrenal medulla (6) and stimulates the pituitary-adrenal axis, resulting in an elevation of plasma corticosterone (7). Although catecholamines and corticosteroids enhance lung maturation, preliminary studies on the incidence of respiratory distress syndrome in premature infants born to cocaine-abusing mothers are conflicting (8, 9). Lung growth and maturation are affected by multiple variables that cannot be isolated in a clinical study. We therefore decided to investigate the effect of intrauterine cocaine exposure on fetal lung maturation in an animal model. MATERIALS AND METHODSThe animal experiments described in this paper were performed with the highest standards of humane care.Five pregnant New Zealand White rabbits (Camm Research, Wayne, NJ) were injected with cocaine hydrochloride U.S.P. (Mallinckrodt, Paris, ICY) at a dose of 18 mg/kg/d S.C. on d 24, 25, and 26 of gestation (77 to 84% of total gestational period). Simultaneously, a control group of five pregnant dams was injected with an equal volume of 0.9% NaC1. Urine was sampled daily between 12 and 24 h after each injection....

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“…Cocaine may affect language development through alterations in the developing monoaminergic neurotransmitter systems (Mayes, 1994(Mayes, , 1999 and through indirect pathways related to cocaine-associated maternal hypertension, decreased uterine blood flow, fetal vasoconstriction and hypoxemia (Mayes, 1994;Moore et al, 1986;Volpe, 1992;Zuckerman and Frank, 1992b) and nutritional deficiencies (Church et al, 1998;Frank et al, 1990;Jacobson et al, 1994;Zuckerman et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

Bandstra

Vogel

Morrow

et al. 2004

Substance Use & Misuse

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The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaineexposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child's age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = −0.071, 95% CI = −0.133, −0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaineassociated deficit was independent of multiple alternative suspected sources of variation in language performance, including other potential responses to prenatal cocaine exposure, such as child's intellectual functioning, and other birth and postnatal influences, including language stimulation in the home environment.

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Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus

Cited by 250 publications

References 9 publications

Effects of Cocaine on Rat Embryo Development in Vivo and in Cultures

Effects of Cocaine on Rat Embryo Development in Vivo and in Cultures

Enhanced Lung Maturation in Cocaine-Exposed Rabbit Fetuses

Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

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