PATHOPHYSIOLOGIC RESPONSES TO FETAL CARDIAC SURGERY

胎儿心脏手术的病理生理反应

• 批准号: 2221008
• 负责人: FRANK HANLEY
• 金额: $ 16.39万
• 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 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2221008
• 关键词: acidosis; cardiovascular pharmacology; congenital heart disorder; embryo /fetus hypoxia; embryo /fetus monitoring; embryo /fetus surgery; heart /lung bypass; heart surgery; pregnancy circulation; radiotracer; respiratory gas transport; sheep; technology /technique development; vascular resistance

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.

该项目的目标是促进胎儿的发育， 心脏手术 某些先天性心脏缺陷是无法纠正后， 出生时，受这些缺陷影响的婴儿预后不良。 为 这些缺陷中有一些是子宫内的明显优势 矫正手术 心脏缺陷的直接胎儿外科干预需要 了解手术干预的生理效应， 体外循环（CPB）对胎儿的影响。 目前，这些影响是 然而，人们对这三种重要的生理反应知之甚少， 胎儿存活率有限。 这些反应是：（1） 胎儿CPB前阶段胎儿心血管稳态丧失 干预，导致缺氧，高碳酸血症和乳酸酸中毒。 2)机构中胎儿血管阻力的“阶跃函数”上升 胎儿体外循环，与胎儿急性失代偿有关 呼吸气体交换，和3）逐渐和持续的上升， 胎儿CPB期间和之后的胎盘血管阻力，导致 降低胎盘血流和胎儿死亡。 该项目的具体重点是确定调解人和 详细的病理生理机制，这三个反应，与眼睛 这些信息的临床应用。 所有实验系列 将使用高度仪器化的胎羊CPB模型进行， 允许对器官进行连续的在线血液动力学监测评估 使用放射性标记的微球的特异性和局部血流，以及 评估各种压力、激素和代谢反应。 中的每 将系统地评价这三种重要的生理反应。 检查CPB前问题的实验将集中在 胎儿应激反应和麻醉剂在引起 胎儿心血管稳态的变化。 实验研究 胎儿血管阻力的“阶跃函数”上升将评估 泵预充溶液被认为是 这个回应。 研究胎盘中 阻力将集中在各种缩血管类花生酸的作用 这些产品被认为是这种反应的介质。 识别这些不良反应的介质和机制 胎儿手术干预和CPB将允许制定合理的 在临床环境中避免或最小化这些问题的方法。