FETAL CIRCULATORY RESPONSE TO CEREBRAL COMPRESSION

当胎儿头部扩张宫颈时， 和骨盆结构的变化 因为胎儿顺从 这些力会导致颅内压（ICP）大大超过 羊水压力，从而降低脑灌注压。 因此，脑血流量（CBF）可能会减少。 保护CBF的机制 可能对分娩过程中的胎儿至关重要 因为胎儿的大脑 当灌注压升高时， 减少，我们推断胎儿将严重依赖增加 维持CBF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一种 动脉压显著增加33%，而不减少胎盘 血流 更令人惊讶的是，这种升压反应 有效地保留胎羊的CBF和脑O2摄取， 产后羔羊和绵羊。 本提案的总体目标是 探讨胎儿这种升压反应的机制 羔羊 首先，我们将研究胎儿的循环反应， 在分娩过程中可能出现的ICP升高。 我们将 确定胎儿头部的外部压迫是否会产生严重的 升压反应，维持脑灌注一样有效， 1例因输注脑脊液而导致颅内压升高。 此外，我们将确定升压反应的动态方面 颅内压反复间歇性升高 接下来，我们将确定 神经体液效应机制。 我们将测试加压素和 血管紧张素系统增强交感肾上腺激活， 胎儿的大量外周血管收缩反应。 出生后 动物，我们观察到选择性区域血管舒张。 我们将 确定这种血管舒张是否是由于一个成熟的发展， β肾上腺素能机制 最后，我们将检验胎儿 更有力地抵御CBF的减少，因为大脑 在相对更缺氧的子宫内环境中操作， 高碳酸血症比产后条件。 这些研究对于 了解胎儿如何应对头部压力的机制 在正常分娩过程中的压迫。 这也许并不 巧合是，初步数据显示最有效的库欣反应是 在胎儿中。 库欣反应提供的保护可能是 对于头部相对较大的人类胎儿尤其重要， 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.