PATHOPHYSIOLOGIC RESPOSE TO FETAL CARDIAC SURGERY

对胎儿心脏手术的病理生理反应

• 批准号: 6389112
• 负责人: FRANK HANLEY
• 金额: $ 34.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 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 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389112
• 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。某些先天性缺陷出生后无法纠正 宫内矫正手术有明显的优势。这 方法需要了解手术的生理效应 对胎儿的干预和体外循环。我们在这个领域的工作 迄今为止，我们已经对以下问题有了实质性但不完整的了解： 这些问题。限制胎儿的三大病理生理反应 干预和体外循环后的生存率（我们 最初的拨款提案中确定的）包括： 1. 胎儿的丧失 胎儿干预前搭桥阶段的心血管稳态。 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搭桥术。 3、逐渐上升 胎儿搭桥期间和之后的胎盘血管阻力，导致 胎盘血流量减少。 该项目的具体重点仍然如最初提案中所述， 确定这些介质的介质和详细的病理生理机制 着眼于该信息的临床应用的三个回应 推动人类胎儿心脏手术的发展。三者中的每一个 将对答复进行系统评估。实验检验 预绕道问题将集中于胎儿应激反应的作用。更远 目前对这种反应的理解受到我们的胎儿动物模型的限制 （羊）。我们建议研究麻醉麻醉在钝化中的功效 仪器化灵长类动物模型中的应激反应。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抑制这种响应。我们的 方法将包括超声波流量传感器来连续测量 除了我们更具体的之外，器官流量的瞬时变化 微球技术不具备这种能力。表彰 影响胎盘血管系统的多种因素，实验 解决搭桥后胎盘阻力逐渐上升的问题将检查 胎盘血管功能障碍的作用除了作用 类二十烷酸。