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.
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