THE EFFECTS OF COCAINE ON FETAL OXYGENATION

可卡因通过干扰产生血压和心率增加 肾上腺素能神经对去甲肾上腺素的摄取和降解 终点站。我们实验室的动物研究表明，静脉注射 可卡因在孕妇体内产生的全身反应比 未怀孕的绵羊，伴随着子宫血流减少和 胎儿血氧水平。我们的研究基于以下假设：1) 静脉注射可卡因的全身心血管反应在 在非怀孕状态下观察到的怀孕情况。2)怀孕的子宫， 与平行的血管床(后肢)相比，主要目标是 可卡因的作用器官。3)妊娠子宫对 可卡因是由去甲肾上腺素和5-羟色胺受体介导的。4)胎儿 氧的利用直接受到可卡因诱导的 子宫血流。第一阶段(产妇)研究将在 妊娠母羊，产后重复两周，对比妊娠和 对可卡因的非妊娠反应。怀孕100天的怀孕绵羊 将接受动静脉插管和开胸手术 放置肺动脉血流探头测量母体血气 心率、血压、心输出量与全身性心功能的计算 血管阻力。在十天后的第二次手术中，流动探头将 确保孕妇股动脉和子宫血流的测量，并 胎儿动脉和静脉导管将放置用于胎儿血液 血压、心率和血气(P02、02含量、pC02、pH)水平。 分级剂量的可卡因将被随机给予静脉或 以确定可卡因对母体的影响 全身血管阻力、子宫和股动脉血流及血管 抵抗。孕妇和胎儿血浆可卡因水平的分析将 定义胎儿和母体隔室的分布和半衰期。 可卡因完全阻断肾上腺素能后给予可卡因 用Katanserin阻断苯氧苯甲胺和5-羟色胺能有助于确定 可卡因引起子宫血管收缩的机制。两周 产后将用可卡因对母羊进行重新测试，以确定全身和 非孕期外周血管反应。在第二阶段 110天内(胎儿)手术器械的研究将包括 母体股动脉和静脉、胎儿脐静脉和胎儿的导管 胎儿主动脉和胎儿上放置电磁流量探头 测定脐带血流量的髂内总动脉。从… 这些测量，胎儿-胎盘心血管功能，可卡因 蓄积，向胎儿输送氧气和提取胎儿氧气和 将在单次和重复的母体或 直接给胎儿注射可卡因。来自于此的复合数据 综合研究将提供有关可卡因风险的新信息 在怀孕期间使用。

Cocaine produces increases in blood pressure and heart rate by interfering with the uptake and degradation of norepinephrine at adrenergic nerve terminals. Animal studies in our laboratory suggest that intravenous cocaine produces greater systemic responses in the pregnant than nonpregnant sheep which are accompanied by reduced uterine blood flow and fetal oxygen levels. Our study is based on the hypotheses that: 1) the systemic cardiovascular response to intravenous cocaine is greater during pregnancy than observed in the non-pregnant state. 2) The pregnant uterus, when compared with a parallel vascular bed (hind limb) is a primary target organ for cocaine action. 3) The response of the pregnant uterus to cocaine is mediated by norepinephrine and serotonin receptors. 4) Fetal oxygen utilization is directly affected by cocaine-induced reductions in uterine blood flow. Phase I (maternal) studies will be conducted in the pregnant ewe and repeated two weeks postpartum to contrast the pregnant and nonpregnant response to cocaine. At 100 days of gestation pregnant sheep will undergo arterial and venous catheterization and thoracotomy for placement of a pulmonary artery flow probe for measurement of maternal heart rate, blood pressure, cardiac output and calculation of systemic vascular resistance. In a second surgery ten days later, flow probes will be secured for maternal femoral and uterine blood flow measurements and fetal arterial and venous catheters will be placed for fetal blood pressure, heart rate, and blood gas (p02, 02 content, pC02, pH) levels. Cocaine in graded doses will be randomized and given intravenously or locally into the uterine artery to determine cocaine effects on maternal systemic vascular resistance, uterine and femoral blood flow and vascular resistance. Analysis for maternal and fetal plasma cocaine levels will define distribution and half life in the fetal and maternal compartments. Cocaine administration following complete alpha adrenergic blockade with phenoxybenzamine and serotonergic blockade with Katanserin will help define the mechanism of cocaine induced vasoconstriction in the uterus. Two weeks postpartum the ewes will be retested with cocaine to determine systemic and peripheral vascular response in the non-pregnant state. In Phase II (fetal) studies surgical instrumentation at 110 days will consist of catheters in the maternal femoral artery and vein, fetal umbilical vein and fetal aorta and placement of an electromagnetic flow probe on the fetal common internal iliac artery for umbilical blood flow determinations. From these measurements, fetal-placental cardiovascular function, cocaine accumulation, oxygen delivery to the fetus and fetal oxygen extraction and consumption will be evaluated during single and repetitive maternal or direct fetal cocaine administration. The composite data from this comprehensive study will provide new information on the risks of cocaine use during pregnancy.