CLINICAL VALIDATION OF TISSUE OXYGEN INDEX IN NEONATES (PRENATAL GROUP)

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。脑损伤仍然是高危新生儿的一个重要问题，包括早产儿1000g和接受复杂心脏手术的新生儿。尽管术中因素的处理可以改善心脏手术期间的神经发育结果，但对于具有高度复杂问题的新生儿，还需要进一步的改进。此外，尽管医疗护理有所改善，但早产儿仍有严重的神经发育异常。乔纳斯博士对先天性心脏病婴儿的神经损伤进行的研究发现，当引入脑血管收缩搭桥策略时，有一部分有脑盗血风险的患者(由于低阻力竞争回路导致血流从大脑转移)有神经损伤的风险。早产儿可能会暴露于动脉导管的脑盗窃和吲哚美辛治疗引起的血管收缩。血流动力学不稳定时期的神经学检查和手术操作是困难的。近红外光谱(NIRS)提供了脑氧合和血管反应性的测量，已被证明与急性神经状态和随后的临床结果相关。直到最近，NIRS的一个主要限制是无法进行实时监测。最近的发展通过在线计算TOI的能力解决了这一限制。乔纳斯博士在动物模型中表明，TOI是神经损伤的预测指标，可以用来指导改善大脑氧合的治疗。TOI尚未在临床环境中进行研究。在当今时代，大多数患有心脏病的婴儿有望在手术中存活下来。这些婴儿中有相当大比例有多种障碍，要么与相关的出生缺陷有关，要么与神经发育障碍有关。手头的问题是确定损害在多大程度上与有限的潜在损害和后天损害有关。虽然手术中的支持方法受到了极大的关注，但很少有人关注心脏病胎儿异常循环中氧气供应和血液流动的改变可能对大脑发育的作用。胎儿血流分布的自动调节变化通过脑血管扩张将更多的血流引导到大脑，被称为脑保留，是胎儿宫内生长受限或子宫胎盘异常的神经发育障碍的预测指标。这些血流分布与不良结局和神经发育异常有关。确定由宫内因素引起的神经发育潜力受损的预测因素与由获得性损害造成的神经发育潜力受损的预测因素，对于先天性心脏病婴儿的护理是至关重要的。多诺里奥博士已经证明，患有复杂先天性心脏病的胎儿会保留大脑。超声心动图可以可靠地识别血流的改变。完全静脉混合液引起的全身性动脉低氧血症，或因主动脉顺行灌注受阻并从动脉导管逆行灌流主动脉弓而导致的体动脉灌注受限的胎儿，可发生向脑的血流重分配。这些改变如何影响子宫内的脑氧合和神经发育结果还有待确定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brain injury continues to be an important problem for high-risk neonates including premature infants 1000g and neonates undergoing complex cardiac surgery. Although manipulation of intraoperative factors can improve neurodevelopmental outcomes during cardiac surgery, further improvements are required for neonates with highly complex problems. In addition, premature infants continue to have significant neurodevelopmental abnormalities despite improvements in medical care. Studies by Dr. Jonas investigating neurological injury in infants with congenital heart disease have identified a subgroup of patients at risk for cerebral steal (shift of blood flow away from the brain due to a low resistance competing circuit) to be at risk for neurological injury when a cerebral vasoconstricting bypass strategy was introduced. Premature infants may be exposed to a cerebral steal from the ductus arteriousus and vasoconstriction from indomethacin therapy.The neurological examination during times of hemodynamic instability and operative procedures is difficult. Near Infrared Spectroscopy (NIRS) provides measurement of cerebral oxygenation and vascular reactivity that has been shown to correlate with acute neurological status and subsequent clinical outcomes. Until recently, a major limitation of NIRS has been an inability for real-time monitoring. Recent developments have addressed this limitation with the ability to make online calculations of the TOI. Dr. Jonas in an animal model has shown that TOI is a predictor of neurological injury and can be used to guide treatment to improve cerebral oxygenation. TOI has not been investigated in the clinical setting. In the current era, the majority of babies with heart disease are expected to survive surgery. A significant percentage of these infants have multiple handicaps, either related to associated birth defects, or to neurodevelopmental compromise. The issue at hand is to determine how much of the impairment is related to limited potential versus acquired damage. While significant attention has been directed towards the method of support during surgery, little attention has been directed at the role that altered oxygen delivery and blood flow attending the abnormal circulation in fetuses with heart disease may have on brain development. Autoregulatory changes in fetal blood flow distribution which directs more blood flow to the brain by cerebral vasodilation has been termed "brain sparing" and is a predictor of neurodevelopmental impairment in fetuses with intrauterine growth restriction or uteroplacental abnormalities. These flow distribution have been correlated with poor outcome and abnormalities in neurodevelopment. The identification of the predictors of impaired neurodevelopmental potential due to in-utero factors, versus those caused by acquired damage, is fundamental to the care of infants with congenital heart disease. Dr. Donofrio has demonstrated that brain sparing occurs in fetuses with complex congenital heart disease. Alterations in blood flow were reliably identified by echocardiography. Redistribution of blood flow toward the brain occurred in fetuses with systemic arterial hypoxemia caused by complete venous admixture, or limited systemic arterial perfusion caused by obstruction to antegrade aortic perfusion with retrograde perfusion of the aortic arch from the ductus arteriosus. How these alterations effect cerebral oxygenation in-utero and neurodevelopmental outcome has yet to be determined.