FETAL CIRCULATORY RESPONSE TO CEREBRAL COMPRESSION

当胎头扩张宫颈时，相当大的力施加在它身上。 以及分娩时的盆腔结构。因为顺从的胎儿 颅骨，这些力量会导致颅内压(ICP)大大超过 羊水压力，从而降低脑灌流压。 因此，脑血流量(CBF)可能减少。保存CBF的机制 很可能在分娩过程中对胎儿至关重要。因为胎儿的大脑 血管在灌流压力下扩张的能力似乎是有限的。 减少，我们推断胎儿将严重依赖于增加 维持脑血流量的动脉压，并引起经典的库欣反应。 当颅内压升高时，我们发现胎羊可以产生 在不影响胎盘的情况下，动脉压显著增加33% 血液流动。更令人惊讶的是，这种升压反应 在保存胎羊脑血流量和脑氧摄取方面效果优于 出生后的羔羊和绵羊。这项提案的总体目标是 探讨胎儿这种升压反应的机制 小羊羔。首先，我们将研究胎儿的循环反应 在可能发生在分娩期间的条件下，颅内压升高。我们会 确定胎头的外部压迫是否会产生深刻的 维持脑灌注的升压反应与 脑脊液输注致颅内压升高1例。 此外，我们还将确定加压反应的动态方面 在反复、间歇性的颅内压升高期间。接下来，我们将确定 神经体液效应机制。我们将测试后叶加压素和 血管紧张素系统正在增强交感神经-肾上腺的激活，以产生 胎儿的大规模外周血管收缩反应。在出生后 动物，我们观察到了选择性的局部血管扩张。我们会 确定这种血管扩张是否是由于 β肾上腺素能机制。最后，我们将测试这样一种想法：胎儿 更有力地防御CBF的减少，因为大脑 在相对低氧和低氧的宫内环境中运行 高碳酸血症而不是出生后的情况。这些研究对以下方面具有重要意义 了解胎儿如何应对头部压力的机制 在正常分娩和分娩过程中受压。也许不是 巧合的是，初步数据显示，库欣反应最有力的是 在胎儿时期。库欣回应提供的保护可能是 对人类胎儿来说尤其重要，因为它的头部相对较大， 头盖骨。

Considerable forces are exerted on the fetal head as it dilates the cervix and pelvic structures during parturition. Because of the compliant fetal skull, these forces can cause intracranial pressure (ICP) to greatly exceed amniotic fluid pressure, thereby decreasing cerebral perfusion pressure. Thus, cerebral blood flow (CBF) could decrease. Mechanisms to preserve CBF are likely to be critical to the fetus during labor. Because fetal brain vessels appear to have a limited ability to dilate when perfusion pressure is reduced, we reasoned that the fetus would rely heavily on increasing arterial pressure to sustain CBF and evoke the classic Cushing response. When ICP was elevated, we found that fetal lambs could generate a remarkable 33% increase in arterial pressure without curtailing placental blood flow. More surprising is that this pressor response is more effective in preserving CBF and cerebral O2 uptake in fetal lambs than in postnatal lambs and sheep. The overall goal of this proposal is to investigate the mechanisms involved in this pressor response in fetal lambs. First, we will investigate the fetal circulatory response to elevated ICP under conditions which would occur during labor. We will determine if external compression of the fetal head generates a profound pressor response that sustains cerebral perfusion as effectively as is the case when ICP is increased by infusion of cerebrospinal fluid. Furthermore, we will determine the dynamic aspects of the pressor response during repetitive, intermittent increases in ICP. Next, we will identify neurohumoral effector mechanisms. We will test whether the vasopressin and angiotensin systems are augmenting sympathoadrenal activation to produce the massive peripheral vasoconstrictor response in the fetus. In postnatal animals, we have observed selective regional vasodilation. We will determine if this vasodilation is due to the maturational development of a beta adrenergic mechanism. Finally, we will test the idea that the fetus more vigorously defends against reductions of CBF because the brain operates in an intrauterine environment that is relatively more hypoxic and hypercapnic than postnatal conditions. These studies are important for understanding the mechanisms of how the fetus copes with the stress of head compression in the process of normal labor and delivery. It is perhaps not coincidental that preliminary data show the most potent Cushing response is in fetus. The protection afforded by a Cushing response is likely to be especially important to the human fetus with its relatively large head and cranium.