Disposition of Cocaine in Pregnant Sheep: II. Physiological Responses

Dj, Burchfield; Rm, Abrams; Miller, R.L.; Cl, DeVane

doi:10.1159/000480572

Cited by 17 publications

(1 citation statement)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The short half-life of cocaine in fetal sheep (4.5 min, DeVane et al, 1991) suggests that the drug would not be present in plasma in measurable amounts 3 days after exposure. During maternal exposure to cocaine, fetuses commonly become hypoxic (Woods et al, 1987;Burchfield et al, 1991b). Marked cerebral hypoxia in fetal lambs can result in delayed seizures (Williams et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Seizures in a Fetal Lamb After Cocaine Exposure: A Case Report

et al. 1992

View full text Add to dashboard Cite

We report the chance observation of two generalized seizures in a fetal lamb that received cocaine. Cocaine was infused intravenously into a 138-day-old fetus while electrocortical (ECoG), electroocular (EOG), and neck electromyographic (EMG) activity were recorded. Fetal rapid eye movement (REM) and nonrapid eye movement (NREM) sleep were disrupted during the cocaine exposure and returned to a normal pattern after infusions were stopped. Seventy-two hours later, however, we recorded generalized seizures with ECoG spike and spike wave activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Seizures in a Fetal Lamb After Cocaine Exposure: A Case Report

et al. 1992

View full text Add to dashboard Cite

show abstract

Ischemia/reperfusion: A new hypothesis for the developmental toxicity of cocaine

1992

View full text Add to dashboard Cite

It has been shown that multiple exposures of gravid rats to cocaine during late gestation result in significant incidences of severe malformations. Hind limb reduction defects were frequent findings in this study. Other studies have shown that comparable abnormalities can be induced in experimental animals by various procedures including vascular clamping, direct fetal exposure to epinephrine, uterine handling following laparotomy, as well as by exposure to hyperbaric oxygen. This paper reviews these and other studies, and presents a novel mechanistic hypothesis that explains their common findings. It is proposed that in each instance, conceptual hypoxia results from hypoperfusion caused by transient vasoconstriction. Following the resumption of normal perfusion, reactive oxygen species are generated by the ischemia/reperfusion mechanisms thought to underlie many pathobiologic lesions. It is proposed that the conceptus is particularly vulnerable to the toxicity of oxygen radicals because of its low antioxidant activities and the highly reduced state of its undifferentiated cells. Sensitivity to cocaine and uterine handling appears to be enhanced during late gestation and it is hypothesized that this results from changes in oxygenation and iron content that increase both the substrate and catalyst for generation of reactive oxygen species.

show abstract

Studies of the role of ischemia/reperfusion and superoxide anion radical production in the teratogenicity of cocaine

et al. 1992

View full text Add to dashboard Cite

The administration of multiple doses of cocaine on a single day during late gestation is teratogenic in rats in which hind limb ectrodactyly is a major finding (Webster and Brown-Woodman, '90). We have previously hypothesized that these limb malformations result from the generation of reactive oxygen species during the process of ischemia/reperfusion in vivo. In order to study the direct effects of cocaine versus the aberrant oxygenation it may induce, we have developed a system for culturing rat embryos between days 14 and 15 of gestation. Growth and development of cultured embryos are comparable to that of in vivo controls. Exposure to normoxia (95% O2) with or without cocaine failed to induce limb malformations and exposure to a single long period of hypoxia (20% O2) only reduced limb growth in the anterior-posterior axis. By contrast, embryos receiving multiple brief exposures to hypoxia developed a significant incidence of hind limb ectrodactyly that appeared indistinguishable from that induced by cocaine in vivo. By incubating day 14 embryos in a nitroblue tetrazolium derivative, 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), it was shown that superoxide anion radical appears in the digital rays following two episodes of reperfusion. Little reaction product was seen under the other conditions. Finally, mitochondrial electron transport particles prepared from teratogenically sensitive limb buds spontaneously "leak" electrons to form superoxide anion radical whereas those from insensitive heart fail to do so. We propose that cocaine and other exposures that can transiently reduce conceptual oxygenation during late gestation are teratogenic by virtue of their capacity to induce ischemia/reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Disposition of Cocaine in Pregnant Sheep: II. Physiological Responses

Cited by 17 publications

References 13 publications

Seizures in a Fetal Lamb After Cocaine Exposure: A Case Report

Seizures in a Fetal Lamb After Cocaine Exposure: A Case Report

Ischemia/reperfusion: A new hypothesis for the developmental toxicity of cocaine

Studies of the role of ischemia/reperfusion and superoxide anion radical production in the teratogenicity of cocaine

Contact Info

Product

Resources

About