PATHOPHYSIOLOGIC RESPONSES TO FETAL CARDIAC SURGERY

描述：(改编自调查人员摘要)这一目标 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是无法纠正的，而且 对于宫内矫正手术来说是一个明显的优势。这种方法 要求并了解外科手术的生理效应 对胎儿的干预和体外循环。我们在中国的工作 到目前为止，这一领域使我们获得了大量但不完整的 对这些问题的理解。三大病理生理 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这一点 建议)包括：1.胎儿心血管动态平衡的丧失 胎儿介入的预搭桥阶段。2.“阶梯函数”的兴起 在胎儿搭桥机构的胎儿血管阻力中 与急性失代偿有关。3.中国经济逐步崛起 胎儿搭桥术中和术后胎盘血管阻力的研究 胎盘血流受阻。 该项目的具体重点仍与原计划相同。 建议，确定介体和详细的病理生理学 着眼于临床探讨这三种反应的机制 应用这些信息促进人的发展 胎儿心脏手术。 将对三份答复中的每一份进行系统评估。 检查预旁路问题的实验将重点放在 胎儿的应激反应。对这一反应的进一步理解 目前受到我们的胚胎动物(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 麻醉在钝化应激反应中的作用 一个仪表化的灵长类动物模型。另外加载独立测量 将应用心功能(电导导管技术) 在此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 在胎儿血管中的阻力将检验这一抑制作用 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，以连续测量 器官血流的瞬时变化除了我们更具体的 不具备这种能力的微球技术。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 阻力将检测胎盘血管内皮细胞的作用 除二十烷醇外，还有损伤的作用。 使用已经开发的信息和技术 在这些研究的过程中，我们将检查胎儿的血流动力学， 转流后的氧耗量和代谢变化。 最后是长期结果(存活率、心功能和器官 将对胎儿搭桥手术后的情况进行研究。

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.