PATHOPHYSIOLOGIC RESPOSE TO FETAL CARDIAC SURGERY

对胎儿心脏手术的病理生理反应

• 批准号: 6536960
• 负责人: FRANK HANLEY
• 金额: $ 35.28万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536960
• 关键词: Primates; anesthesia; cardiac output; cardiovascular pharmacology; catecholamines; congenital heart septum defect; cortisol; disease /disorder model; eicosanoids; embryo /fetus surgery; embryo /fetus therapy; extracorporeal circulation; heart /lung bypass; heart metabolism; heart surgery; histopathology; homeostasis; microcapsule; nonhuman therapy evaluation; placenta disorders; pregnancy circulation; prenatal stress; sheep; ultrasonography; vascular resistance

The goal of this ongoing project is to continue the development of fetal cardiac surgery. Certain congenital defects are uncorrectable after birth and there is a clear advantage for intrauterine corrective surgery. This approach requires an understanding of the physiological effects of surgical intervention and extracorporeal circulation on the fetus. Our work in this area to date has allowed us to gain a substantial but incomplete understanding of these issues. The three major pathophysiological responses which limit fetal survival following intervention and extracorporeal circulation (which we identified in the original grant proposal) include: 1. The loss of fetal cardiovascular homeostasis in the pre-bypass phase of fetal intervention. 2. The "step function" rise in fetal vascular resistance at the institution of fetal bypass which is associated with acute decompensation. 3. The gradual rise in placental vascular resistance during and after fetal bypass which results in depressed placental blood flow. The specific focus of this project remains as stated in the original proposal, to identify the mediators and detailed pathophysiologic mechanisms of these three responses with an eye towards clinical application of this information to advance the development of human fetal cardiac surgery. Each of the three responses will be systematically evaluated. Experiments examining the pre-bypass problem will focus on the role of the fetal stress response. Further understanding of this response is presently limited by our fetal animal model (sheep). We propose to study the efficacy of narcotic anesthesia in blunting the stress response in an instrumented primate model. Experiments addressing the 'step function' rise in fetal vascular resistances will examine the inhibition of this response using specifically designed bypass circuitry. Our methodology will include ultrasonic flow transducers to continuously measure instantaneous changes in organ flow in addition to our more specific microsphere techniques, which do not have this capability. In recognition of the multiple factors effecting the placental vasculature, experiments addressing the gradual rise in post bypass placental resistance will examine the role of placental vascular dysfunction in addition to the role of eicosanoids.

这个正在进行的项目的目标是继续开发 胎儿心脏手术某些先天性缺陷在出生后是无法矫正的 子宫内矫正手术有明显的优势。这 这种方法需要了解外科手术的生理效应， 介入和体外循环。我们在这一领域的工作 到目前为止，已经使我们能够获得一个实质性的，但不完整的理解， 这些问题限制胎儿发育的三大病理生理反应 干预和体外循环后的生存率（我们 在原补助金提案中确定的）包括：1。胎儿丢失 心脏血管稳态在预分流阶段的胎儿干预。2. 胎儿血管阻力的“阶跃函数”上升， 与急性失代偿相关的胎儿旁路。3.逐渐兴起 在胎儿分流术期间和之后的胎盘血管阻力中， 抑制胎盘血流量 该项目的具体重点仍与原提案所述相同， 确定介质和详细的病理生理机制，这些 三种反应着眼于这一信息的临床应用， 促进人类胎儿心脏外科的发展。三个 将对答复进行系统评价。实验研究 分流前的问题将集中在胎儿应激反应的作用。进一步 目前对这种反应的理解受到我们的胎儿动物模型的限制 （绵羊）。我们建议研究麻醉剂麻醉在钝头手术中的效果 灵长类动物模型的应激反应实验寻址 胎儿血管阻力的“阶跃函数”上升将检查 使用专门设计的旁路电路来抑制这种响应。我们 方法将包括超声流量传感器来连续测量 器官流动的瞬时变化，除了我们更具体的 微球技术，其不具有这种能力。以表彰 影响胎盘血管的多因素，实验 解决旁路术后胎盘阻力的逐渐上升将检查 胎盘血管功能障碍的作用，除了作用 类花生酸