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

新生儿组织氧指数的临床验证（产前组）

• 批准号: 7951099
• 负责人: RICHARD A JONAS
• 金额: $ 6.65万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951099
• 关键词: Acute; Address; Admixture; Animal Model; Attention; Blood Circulation; Blood Vessels; Blood flow; Brain; Brain Injuries; Bypass; Cardiac Surgery procedures; Caring; Cerebrum; Clinical; Clinical Research; Complex; Computer Retrieval of Information on Scientific Projects Database; Congenital Abnormality; Development; Disabled Persons; Ductus Arteriosus; Echocardiography; Fetal Growth Retardation; Fetus; Funding; Grant; Hand; Heart Diseases; Hypoxemia; Impairment; Indomethacin; Infant; Infant Care; Institution; Measurement; Medical; Methods; Monitor; Near-Infrared Spectroscopy; Nervous System Trauma; Neurodevelopmental Impairment; Neurologic Examination; Neurological status; Obstruction; Operative Surgical Procedures; Outcome; Oxygen; Patients; Perfusion; Premature Infant; Research; Research Personnel; Resistance; Resources; Risk; Role; Source; Subgroup; Theft; Time; Tissues; United States National Institutes of Health; Validation; Vasodilation; Venous; aortic arch; congenital heart disorder; fetal blood; handicapping condition; hemodynamics; high risk; improved; in utero; indexing; neonate; neurodevelopment; prenatal; vasoconstriction

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 对于高危新生儿（包括早产儿 1000g 和接受复杂心脏手术的新生儿）来说，脑损伤仍然是一个重要问题。 尽管操纵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，还需要进一步改进。 此外，尽管医疗保健有所改善，早产儿仍然存在明显的神经发育异常。 Jonas 博士对患有先天性心脏病的婴儿的神经损伤进行了研究，结果发现，当引入脑血管收缩旁路策略时，存在脑盗血（由于低阻力竞争回路而导致血流远离大脑）风险的患者亚群也面临神经损伤的风险。早产儿可能会受到动脉导管的脑盗血和吲哚美辛治疗引起的血管收缩的影响。血流动力学不稳定和手术过程中的神经系统检查很困难。近红外光谱 (NIRS) 可测量脑氧合和血管反应性，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。 Jonas 博士在动物模型中证明 TOI 是神经损伤的预测因子，可用于指导改善脑氧合的治疗。 TOI 尚未在临床环境中进行过研究。 在当今时代，大多数患有心脏病的婴儿有望在手术后存活下来。 这些婴儿中有很大一部分患有多种障碍，要么与相关的出生缺陷有关，要么与神经发育受损有关。当前的问题是确定有多少损害与有限的潜在损害和后天损害有关。 虽然人们对手术期间的支持方法给予了极大的关注，但很少有人关注改变患有心脏病的胎儿的异常循环的氧气输送和血流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舒张将更多的血流引导至大脑，被称为“大脑保留”，并且是患有宫内生长受限或子宫胎盘异常的胎儿神经发育障碍的预测因子。这些血流分布与神经发育的不良结果和异常相关。确定由宫内因素引起的神经发育潜力受损的预测因子与后天性损伤引起的神经发育潜力受损的预测因子，对于先天性心脏病婴儿的护理至关重要。多诺弗里奥博士证明，患有复杂先天性心脏病的胎儿可以保留大脑。超声心动图可以可靠地识别血流的变化。 流向大脑的血流重新分配发生在因完全静脉混合引起的全身动脉低氧血症的胎儿中，或因顺行主动脉灌注受阻而从动脉导管逆行灌注主动脉弓而引起全身动脉灌注受限的胎儿中。这些改变如何影响子宫内脑氧合和神经发育结果尚未确定。