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COCAINE & FETAL CEREBRAL BLOOD FLOW AND METABOLISM

可卡因

基本信息

批准号：
2120068
负责人：
HISAYO O MORISHIMA
金额：
$ 21.02万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-12-15 至 1994-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2120068
关键词：
aerobiosis blood flow measurement brain metabolism carbohydrate metabolism cocaine electrocardiography electroencephalography electromyography electrooculography embryo /fetus embryo /fetus hypoxia embryo /fetus toxicology oxygen consumption pharmacokinetics pregnancy circulation sheep vasoconstriction

项目摘要

The principal objective of this research project is to determine whether cocaine-induced hypoxemia, cerebral vasoconstriction, and possible increases in oxidative metabolism may combine in the fetus to produce severe fetal brain tissue hypoxia which could induce intrauterine brain injury. In adults, cocaine has known vasoconstrictive effects on the cerebral circulation. Cocaine is known to induce fetal hypoxemia by reducing uterine blood flow; the normal compensatory fetal cerebral vasodilation may be blunted by these vasoconstrictive effects of cocaine, exacerbating tissue hypoxia. In addition, cocaine may increase cerebral oxidative metabolism, which would further compromise tissue oxygenation. In chronically prepared fetal sheep, vascular catheters will be placed in fetal arteries, veins, and superior sagittal sinus and in maternal arteries and veins. Electrodes will be placed for recording fetal electroencephalogram, electrocardiogram, and electromyograms. Cerebral blood flow will be measured with microspheres and cerebral metabolism will be studied by the Fick principle. Cocaine will be infused into mother and fetus to determine the effects on fetal arterial and sagittal sinus oxygenation, cerebral blood flow, cerebral oxidative and carbohydrate metabolism, and fetal behavior. Although cocaine is one of the most popular illicit drugs used during pregnancy, to date very little is known regarding the effects of cocaine on fetal physiology, the metabolic effects of cocaine on the fetal brain, or the effects of cocaine on fetal behavior. The proposed studies assume particular clinical relevance in light of recent observations of a high prevalance of brain structural .abnormalities and microcephaly in cocaine-exposed offspring. These studies will contribute to the understanding of cocaine-induced brain lesions and cocaine effects on fetal and newborn behavior as well as to the understanding of the physiology of the fetal cerebral circulation and the pharmacology of cocaine during pregnancy.

本研究项目的主要目的是确定是否可卡因引起的低氧血症脑血管收缩氧化代谢的增加可能在胎儿中联合收割机产生严重的胎儿脑组织缺氧可导致宫内脑损伤在成人中，可卡因已知对血管收缩作用，脑循环已知可卡因通过以下方式诱导胎儿低氧血症：减少子宫血流量;正常代偿性胎儿脑可卡因的这些血管收缩作用可减弱血管舒张，加剧组织缺氧。此外，可卡因可能会增加大脑氧化代谢，这将进一步损害组织氧合。在长期准备的胎羊中，将血管导管放置在胎儿动脉、静脉、上级矢状窦和母体动脉和静脉。将放置电极记录胎儿脑电图心电图和肌电图脑将用微球测量血流量，用Fick原理来研究。将皮质醇注入母亲体内，确定对胎儿动脉和矢状窦的影响氧合、脑血流量、脑氧化和碳水化合物新陈代谢和胎儿行为。虽然可卡因是最流行的非法药物之一，怀孕，到目前为止，关于可卡因的影响知之甚少，胎儿生理学，可卡因对胎儿大脑的代谢影响，或可卡因对胎儿行为的影响拟议的研究假设特别是临床相关性，鉴于最近观察到的高脑结构异常和小头畸形的患病率可卡因暴露的后代这些研究将有助于了解可卡因引起的脑损伤和可卡因对胎儿的影响和新生儿的行为，以及对生理学的理解，胎儿脑循环和可卡因的药理学怀孕