PATHOPHYSIOLOGIC RESPONSES TO FETAL CARDIAC SURGERY

胎儿心脏手术的病理生理反应

• 批准号: 2430687
• 负责人: FRANK HANLEY
• 金额: $ 20.05万
• 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 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430687
• 关键词: Macaca mulatta; anesthesia; angiocardioultrasonography; animal mortality; cardiovascular pharmacology; catecholamines; congenital heart septum defect; cortisol; eicosanoids; embryo /fetus surgery; endothelin; female; heart /lung bypass; heart metabolism; heart surgery; histopathology; lactates; oxygen consumption; postoperative state; pregnancy circulation; prenatal stress; preoperative state; radioactive microsphere technique; respiratory gas transport; sheep; vascular resistance

DESCRIPTION: (Adapted from investigator's abstract) The goal of this ongoing project is to continue the development of fetal cardiac surgery. Certain congenital heart defects are uncorrectable after birth and there is a clear advantage for intrauterine corrective surgery. This approach requires and 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 in presently limited by our fetal animal (sheep) and by the methodology of measuring the fetal cardiac response to stress. We propose to study the efficacy of narcotic anesthesia in blunting the stress response in an instrumented primate model. Additionally load independent measurements of cardiac function (the conductance catheter technique) will be applied in this model in order to directly measure myocardial functional response to stress. 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 miscrosphere techniques which do not have this capability. In recognition of the multiple factors affecting the placental vasculature, experiments addressing the gradual rise in post bypass placental resistance will examine the role of placental vascular endothelial injury in addition to the role of eicosanoids. Using the information and techniques which have been developed in the course of these studies we will then examine the fetal hemodynamics, oxygen consumption, and metabolic changes in the post bypass period. Finally the long term outcome (survival, ventricular function, and organ pathology) following fetal bypass will be studied.

描述：（改编自研究者的摘要）本研究的目标 正在进行的项目是继续开发胎儿心脏手术。 某些先天性心脏病在出生后无法纠正，并且 是宫内矫正手术的明显优势。这种做法 需要并了解手术的生理效应 对胎儿的干预和体外循环。我们的工作在 迄今为止，这一领域已使我们获得了大量但不完整的成果 对这些问题的了解。三大病理生理学 干预后限制胎儿存活的反应和 体外循环（我们在最初的拨款中确定了 建议）包括： 1. 胎儿心血管稳态的丧失 胎儿干预的预绕道阶段。 2.“阶跃函数”上升 在胎儿搭桥机构中胎儿血管阻力 与急性失代偿有关。 3. 逐渐上升 胎儿搭桥期间和之后的胎盘血管阻力，导致 胎盘血流抑制。 该项目的具体重点仍如最初所述 建议，以确定介质和详细的病理生理学 这三种反应的机制着眼于临床 应用这些信息来促进人类的发展 胎儿心脏手术。 这三个答复中的每一个都将得到系统评估。 检查预旁路问题的实验将集中于 胎儿的应激反应。进一步了解此响应 目前受到我们的胎儿动物（羊）和方法的限制 测量胎儿心脏对压力的反应。我们建议学习 麻醉麻醉在减弱应激反应方面的功效 仪器化灵长类动物模型另外，与负载无关的测量 将应用心脏功能（电导导管技术） 在该模型中为了直接测量心肌功能 对压力的反应。针对“阶跃函数”上升的实验 在胎儿血管阻力中将检查这种抑制 使用专门设计的旁路电路进行响应。我们的方法论 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。在 认识影响胎盘脉管系统的多种因素， 针对绕道后胎盘逐渐升高的实验 电阻会检查胎盘血管内皮的作用 除了类二十烷酸的损伤作用外。 使用已开发的信息和技术 在这些研究过程中，我们将检查胎儿的血流动力学， 绕道后阶段的耗氧量和代谢变化。 最后是长期结果（生存、心室功能和器官） 将研究胎儿搭桥后的病理学）。