PATHOPHYSIOLOGIC RESPONSE TO FETAL CARDIAC SURGERY

这个正在进行的项目的目标是继续发展胎儿 心脏手术。某些先天缺陷在出生后是无法矫正的。 而且宫内矫正手术有一个明显的优势。这 这种方法需要了解以下因素的生理影响 胎儿的外科干预和体外循环。我们的 到目前为止，这方面的工作使我们能够在 对这些问题的认识不全面。三大 限制胎儿存活的病理生理反应 干预和体外循环(我们在 最初的赠款提案)包括：1.胎儿心血管疾病的损失 转流前胎儿干预中的动态平衡。2.“阶梯” 功能：胎儿血管阻力在胎儿期升高 与急性失代偿相关的旁路。3.逐步崛起 胎儿搭桥术中和术后胎盘血管阻力的变化 导致胎盘血流量下降。 该项目的具体重点仍与原计划相同。 建议，确定详细的病理生理的介体 着眼于临床探讨这三种反应的机制 应用这些信息促进人类胚胎发育 心脏手术。这三个答复中的每一个都将是系统的 已评估。检测预旁路问题的实验将集中在 胎儿应激反应的作用。对这种反应的进一步理解 目前受到我们胎儿动物模型(绵羊)的限制。我们建议 麻醉钝化应激反应的效果研究 在工具性灵长类动物模型中。解决“步骤”问题的实验 胎儿血管阻力的功能上升将检查这种抑制 使用专门设计的旁路电路来实现这一响应。我们的 方法将包括超声波流量传感器，以连续 除了我们的更多信息外，还可以测量器官血流的瞬时变化 没有这种能力的特定微球技术。在……里面 对影响胎盘血管系统的多种因素的认识， 解决搭桥术后胎盘逐渐增加的实验 阻力将研究胎盘血管功能障碍在 此外还有二十烷类化合物的作用。

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 by 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 of detailed pathophysiological 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 these 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 instrumental 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.