PATHOPHYSIOLOGIC RESPOSE TO FETAL CARDIAC SURGERY

这个正在进行的项目的目标是继续开发 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 治疗方法需要了解外科手术的生理效应。 对胎儿的干预和体外循环。我们在这方面的工作 到目前为止，我们已经获得了大量但不完整的理解 这些问题。限制胎儿发育的三大病理生理反应 介入和体外循环后的存活率(我们 在最初的赠款提案中确定的)包括：1.胎儿的损失 胎儿介入搭桥前阶段的心血管动态平衡。2. 胎儿血管阻力的“阶梯函数”升高 胎儿搭桥术与急性失代偿相关。3.逐步崛起 在胎儿搭桥术期间和术后胎盘血管阻力的变化 胎盘血流受阻。 这一项目的具体重点仍与原提案中所述相同， 以确定这些疾病的介质和详细的病理生理机制 着眼于将这一信息应用于临床的三种反应 推动人类胎儿心脏外科的发展。三个人中的每一个 将对答复进行系统评估。实验检验了 预搭桥问题将重点放在胎儿应激反应的作用上。进一步 对这种反应的理解目前受到我们的胎儿动物模型的限制 (绵羊)。我们建议研究麻醉在钝性手术中的效果。 仪器化灵长类动物模型中的应激反应。实验寻址 胎儿血管阻力的“阶跃函数”上升将检查 使用专门设计的旁路电路抑制这种响应。我们的 方法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 微球技术，没有这种能力。承认…… 影响胎盘血管系统的多因素实验 解决搭桥术后胎盘阻力逐渐上升的问题将检查 胎盘血管功能障碍的作用 二十烷类化合物。

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 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 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 instrumented 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.