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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。脑损伤仍然是高危新生儿的一个重要问题，包括早产儿1000克和接受复杂心脏手术的新生儿。虽然操作术中因素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，需要进一步改善。此外，尽管医疗保健有所改善，早产儿仍有明显的神经发育异常。乔纳斯博士对先天性心脏病婴儿神经损伤的研究发现，当引入脑血管收缩旁路策略时，有脑偷窃风险（由于低阻力竞争回路导致血流远离大脑）的患者亚组有神经损伤的风险。早产儿可能暴露于动脉导管的脑偷盗和因吲哚美辛治疗引起的血管收缩。在血流动力学不稳定和手术过程中进行神经学检查是困难的。近红外光谱（NIRS）提供脑氧合和血管反应性的测量，这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，近红外光谱的一个主要限制是无法进行实时监测。最近的发展已经通过在线计算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，可用于指导治疗以改善脑氧合。TOI尚未在临床环境中进行调查。在当今时代，大多数患有心脏病的婴儿都有望在手术中存活下来。这些婴儿中有相当大比例有多种残疾，要么与相关的出生缺陷有关，要么与神经发育损害有关。目前的问题是确定有多少损害与有限潜在损害和获得性损害有关。虽然手术期间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血液循环异常导致的氧气输送和血流改变对大脑发育的影响。胎儿血流分布的自我调节变化，通过脑血管舒张引导更多的血液流向大脑，被称为“脑保留”，是宫内生长受限或子宫胎盘异常胎儿神经发育障碍的预测指标。这些血流分布与预后不良和神经发育异常有关。鉴别由子宫内因素引起的神经发育潜力受损与后天损伤引起的神经发育潜力受损的预测因素，对先天性心脏病婴儿的护理至关重要。多诺弗里奥博士已经证明，大脑保留发生在患有复杂先天性心脏病的胎儿身上。超声心动图可靠地识别出血流的改变。静脉完全混合引起的全身性动脉低氧血症，或动脉导管逆行灌注导致主动脉顺行灌注阻塞导致全身性动脉灌注受限的胎儿，血流会重新流向脑部。这些改变如何影响子宫内的脑氧合和神经发育结果尚未确定。

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.