PATHOPHYSIOLOGIC RESPONSES TO FETAL CARDIAC SURGERY

这个项目的目标是为胎儿的发展做出贡献 心脏手术。某些先天心脏缺陷是无法纠正的 出生，受这些缺陷影响的婴儿预后很差。为 这些缺陷中的一些对于子宫内有明显的优势 矫正手术。 心脏缺陷的直接胎儿外科干预需要 对手术干预的生理学效应的认识 胎儿体外循环(CPB)。目前，这些影响是 然而，人们对三种重要的生理反应知之甚少 胎儿存活的极限已经被确定。这些回应是：1) 围术期胎儿心血管内稳态的丧失 干预，导致缺氧、高碳酸血症和乳酸酸中毒。 2)该机构胎儿血管阻力的“阶梯函数”上升 胎儿体外循环，与胎儿急性失代偿有关 呼吸性气体交换，以及3)逐渐和持续的上升 胎儿体外循环期间和术后胎盘血管阻力，导致 胎盘血流受阻和胎儿死亡。 本项目的具体重点是确定和的调解人 这三种反应的详细病理生理机制，带一只眼睛 这一信息的临床应用。所有实验系列 将使用高度仪器化的胎羊体外循环模型进行手术， 允许对器官进行连续在线血流动力学监测和评估 使用放射性标记微球的特定和局部血流，以及 评估各种压力、荷尔蒙和代谢反应。每一个 这三个重要的生理反应将被系统地评估。 检查体外循环前问题的实验将集中在 胎儿应激反应和麻醉剂在引起胎盘破裂中的作用 胎儿心血管动态平衡的变化。实验检验了 胎儿血管阻力的“阶跃功能”上升将评估 泵启动溶液被认为是 这样的回应。检测胎盘逐渐升高的实验 耐药性将集中在各种收缩血管的二十烷类化合物的作用上 被牵连为这一反应的调解人的产品。 识别这些有害反应的介体和机制 对胎儿手术的干预和CPB的合理开展将使 在临床环境中避免或尽量减少这些问题的方法。

The goal of this project is to contribute to the development, of fetal cardiac surgery. Certain congenital heart defects are uncorrectable after birth, and infants affected with these defects have a poor prognosis. For some of these defects there is a clear advantage for intra-uterine corrective surgery. Direct fetal surgical intervention for heart defects requires an understanding of the physiologic effects of surgical intervention and cardiopulmonary bypass (CPB) on the fetus. At present these effects are poorly understood, however three important physiologic responses which limit fetal survival have been identified. These responses are: 1) the loss of fetal cardiovascular homeostasis in the pre-CPB phase of fetal intervention, which results in hypoxia, hypercarbia, and lactic acidosis. 2) the "step-function" rise in fetal vascular resistance at the institution of fetal CPB, which is associated with acute decompensation of fetal respiratory gas exchange, and 3) the gradual and sustained rise in placental vascular resistance during and after fetal CPB, which results in depressed placental blood flow and fetal demise. The specific focus of this project is to identify the mediators of and the detailed pathophysiologic mechanisms of these three responses, with an eye towards clinical application of this information. All experimental series will be performed using a highly instrumented fetal lamb CPB model, which allows continuous on line hemodynamic monitoring evaluation of organ specific and regional blood flow using radiolabelled microspheres, and evaluation of various stress, hormonal, and metabolic responses. Each of the three important physiologic responses will be systematically evaluated. Experiments examining the pre-CPB problem will focus on the role of the fetal stress response and the role of anesthetic agents in causing the changes in fetal cardiovascular homeostasis. Experiments examining the "step-function" rise in fetal vascular resistance will evaluate elements in the pump-priming solution which have been implicated as the mediators of this response. Experiments examining the gradual rise in placental resistance will focus on the role of various vasoconstrictive eicosanoid products which have been implicated as mediators of this response. Identification of the mediators and mechanisms of these unwanted responses to fetal surgical intervention and CPB will allow development of a rational approach for avoiding or minimizing these problems in the clinical setting.