PATHOPHYSIOLOGIC RESPONSES TO FETAL CARDIAC SURGERY

描述：（改编自研究者摘要） 目前正在进行的项目是继续发展胎儿心脏手术。 某些先天性心脏缺陷在出生后无法矫正， 是子宫内矫正手术的明显优势。这种方法 需要和理解手术的生理效应 介入和体外循环。我们搞好 迄今为止，这一领域使我们能够获得实质性但不完整的 对这些问题的理解。三大病理生理学 干预后限制胎儿存活的反应， 体外循环（我们在最初的拨款中确定 建议）包括：1.胎儿心血管稳态的丧失 胎儿手术的搭桥前阶段2.“阶梯函数”的兴起 在建立胎儿旁路时， 与急性失代偿有关3.逐渐上升的 在胎儿旁路手术期间和之后的胎盘血管阻力 胎盘血流量下降 本项目的具体重点仍如原文所述 建议，以确定介质和详细的病理生理 这三种反应的机制，着眼于临床 利用这些信息促进人类发展 胎儿心脏手术 将对这三项答复中的每一项进行系统评价。 检查预旁路问题的实验将集中在 胎儿应激反应进一步了解这一反应， 目前受到我们的胎儿动物（绵羊）和方法学的限制， 测量胎儿心脏对压力的反应。我们建议研究 麻醉剂麻醉在减弱应激反应中的作用 一个装有仪器的灵长类动物模型。额外的负载独立测量 心脏功能（电导导管技术）将被应用 在该模型中，为了直接测量心肌功能 对压力的反应。解决“阶跃函数“上升的实验 在胎儿血管阻力将检查这种抑制 响应使用专门设计的旁路电路。我们的方法 将包括超声波流量传感器， 器官流动的瞬时变化，除了我们更具体的 微球技术不具有这种能力。在 认识到影响胎盘血管系统的多种因素， 研究体外循环后胎盘组织中 阻力将检查胎盘血管内皮细胞的作用， 除了类花生酸的作用外， 利用在该领域开发的信息和技术， 在这些研究的过程中，我们将检查胎儿的血流动力学， 氧消耗和旁路后时期的代谢变化。 最后是长期结果（生存率、心室功能和器官功能）， 病理学）。

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.